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Safety and Efficacy of Tideglusib in Congenital or Childhood Onset Myotonic Dystrophy (REACH CDM X)
Howell, Jodie - jodie.howell@vcuhealth.org
Johnson, Nicholas, E
NCT05004129
HM20023901
Inclusion Criteria:
Subjects who do not enter this study directly from completing the AMO-02-MD-2-003 study (i.e. subjects who did not complete AMO-02-MD-2-003, subjects who completed AMO-02-MD-2-003 but did not directly rollover or subjects who are re-entering AMO-02-MD-2-004), will not be considered eligible for the study without meeting all of the criteria below:
• Subjects under study must be individuals with a diagnosis of Congenital or Childhood Onset DM1.
• Diagnosis must be genetically confirmed
• Subjects must be male or female aged ≥6 years to ≤45 years at Screening
• Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1)
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or legally authorized representative (LAR) provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Subjects entering directly from completing the antecedent AMO-02-MD-2-003 study will not be considered eligible for the study without meeting all of the criteria below:
• Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11
• Written, voluntary informed consent must be obtained before any study related procedures are conducted. Where a parent or LAR provides consent, there must also be assent from the subject (as required by local regulations)
• Subject's caregiver must be willing and able to support participation for duration of study
• Subject must be willing and able to comply with the required food intake restrictions as outlined per protocol Key
Exclusion Criteria:
• Body mass index (BMI) less than 13.5 kg/m² or greater than 40 kg/m²
• New or change in medications/therapies within 4 weeks prior to Eligibility/Baseline Visit
• Use within 4 weeks prior to Eligibility/Baseline Visit of strong CYP3A4 inhibitors (eg.clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir)
• Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window (e.g. warfarin and digitoxin)
• Current enrollment in a clinical trial of an investigational drug or enrollment in a clinical trial of an investigational drug in the last 6 months other than the AMO-02- MD-2-003 study
• Existing or historical medical conditions or complications (eg. neurological, cardiovascular, renal, hepatic, gastrointestinal, endocrine or respiratory disease) that may impact the interpretability of the study results
• Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry
DRUG: Tideglusib
Congenital Myotonic Dystrophy
Tideglusib, AMO-02-MD-2-004, Congenital Myotonic Dystrophy, Myotonic Dystrophy, Dystrophia Myotonica, Myotonia Atrophica, Myotonia Dystrophica, Myotonic Dystrophy, Congenital, Steinert Disease, Steinert Myotonic Dystrophy, Steinert's Disease
TruGraf® Long-term Clinical Outcomes Study (TRULO)
Isioma Agboli, MD - isiomaagboli@eurofins-tgi.com
Moinuddin, Irfan
NCT04491552
HM20020284
Inclusion Criteria:
• Written informed consent and HIPAA authorization;
• At least 18 years of age;
• Recipient of a primary or subsequent deceased-donor or living-donor kidney transplant;
• At least 3-months post-transplant;
• Stable serum creatinine (per Principal Investigator);
• Treated with any immunosuppressive regimen, and;
• Selected by provider to undergo OmniGraf™ (TruGraf® and TRAC™) testing as part of post-transplant care; and
Exclusion Criteria:
• Recipient of a combined organ transplant with an extra-renal organ and/or islet cell transplant;
• Recipient of a previous non-renal solid organ and/or islet cell transplant;
• Known to be pregnant;
• Known to be infected with HIV;
• Known to have Active BK nephropathy;
• Known to have nephrotic proteinuria (Per Principal Investigator);
• Participation in other biomarker studies testing clinical utility.
Diagnostic Test: Patients monitored with TruGraf and TRAC testing
Kidney Transplant Rejection
Biomarkers, Subclinical Rejection
Nonalcoholic Fatty Liver Disease in HIV Database
Tinsay A Woreta, MD, MPH - tworeta1@jhmi.edu
Sterling, Richard, K
NCT05023044
HM20023554
Inclusion Criteria:
* Documented HIV infection
* ≥18 of age at time of initial screening
* HIV suppression with HIV RNA \<200 copies/ml on stable ART for ≥ 6 months and no change in ART class for ≥ 3 months, prior to enrollment
* Participants must meet at least one of the following inclusion criteria:
* Histologically confirmed NAFLD \[defined as NAFL (\>5% steatosis, with or without lobular or portal inflammation), borderline NASH or definitive NASH\] within 6 months prior to screening (per local pathology report)
* Liver stiffness measurement (LSM) ≥6 kPa from FibroScan exam performed during screening or within 12 months prior to screening and a diagnosis of NAFLD based on clinical and imaging (FibroScan CAP≥263 dB/m, ultrasound, CT or MRI) diagnosis at any time
* LSM ≥8 kPa from FibroScan exam performed during screening or within 12 months prior to screening, in the absence of CAP ≥263 dB/m
* Able to provide written informed consent to part
* Willingness to be in the study for 1 or more years
* Provision of written informed consent
Exclusion Criteria:
* Positive hepatitis B surface antigen
* Evidence of recent or current hepatitis C virus (HCV) as marked by the presence of anti-HCV antibody with detectable HCV RNA in serum within 3 years prior to enrollment. Participants with anti-HCV antibody positivity who have undetectable HCV RNA 3 years prior to enrollment (either due to spontaneous clearance or clearance with treatment) will be eligible to participate if HCV RNA at entry remains undetected
* Significant alcohol consumption (≥ 3 drinks daily on average in men and ≥ 2 drinks daily on average in women)
* Evidence of other causes of chronic liver disease
* History of prolonged (\> 1 month) total parenteral nutrition within a 6-month period before liver biopsy or before baseline FibroScan VCTE exam
* Short bowel syndrome
* History of biliopancreatic diversion
* History of bariatric surgery within 2 years of enrollment (participants expecting to undergo bariatric surgery can be enrolled prior to the procedure)
* Solid organ transplant recipients
* Other condition that is likely to interfere with study follow-up NAFLD, NASH - Nonalcoholic Steatohepatitis, Hiv
Impella®-Supported PCI in High-Risk Patients With Complex Coronary Artery Disease and Reduced Left Ventricular Function (PROTECT IV)
Charles (Chuck) Simonton, MD FACC FSCAI - csimonton@abiomed.com
NCT04763200
Pending IRB#
Inclusion Criteria:
• Age ≥18 years and ≤90 years
• Clinical presentation and baseline left ventricular function are as follows: Either 2A or 2B must be present A. Subject has CCS or NSTEMI with an LVEF ≤40% NOTE: The LVEF must be quantitatively measured as ≤40% by echo within 30 days assuming no change in clinical condition. If multiple echos have been performed within 30-days, the most recent test must be used to qualify the patient. NOTE: Subject qualifies if the quantitative site read LVEF is ≤30%; if the quantitative site read is \>30% - ≤40% the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment (Core Lab will provide \<48-hour turnaround). Similarly, if the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤40% before subject enrollment. OR B. Subject has STEMI ≥24 hours and \<30 days after symptom onset with an LVEF ≤30% NOTE: In patients qualifying with recent STEMI, the LVEF must be demonstrated to be ≤30% by quantitative echocardiography after the primary PCI procedure (if performed) and within 72-hours prior to the planned randomization. If primary PCI was not performed, the qualifying echocardiogram will be the one taken during the index hospitalization closest to the index procedure. If the site read is qualitative only (i.e., only provides broad ranges without detailed LVEF quantification), the Echo Core Lab must confirm the LVEF is ≤30% before subject enrollment.
• Local heart team (interventional cardiologist and cardiac surgeon) has determined that PCI is indicated and is the most appropriate management for the patient
• Complex PCI will be performed: Either 4A or 4B must be met A. One of the following must be present: i. Triple vessel disease is present (visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89)\] is present in all 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) with PCI planned in ≥2 of these vessels in the proximal or mid LAD, proximal or mid-LCX or proximal, mid- or distal RCA \[i.e., not a branch vessel\]) OR ii. Left main distal bifurcation or trifurcation disease (visually-assessed DS ≥50% \[or DS ≥30% if non-invasive evidence of ischemia in both the anterior and posterolateral distributions or left main IVUS MLA ≤6.0 mm2 or FFR ≤0.80 or iFR ≤0.89\] is present) with planned intervention of the left main plus at least 2 branch vessels (i.e., the ostial LAD, ostial LCX or ostial ramus) OR iii. Left main equivalent disease with both ostial LAD and ostial LCX having visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive evidence of ischemia on a localizing stress test or invasive evidence of ischemia (FFR ≤0.80 or iFR ≤0.89\] and requiring intervention in both branches OR iv. Intervention of the last remaining vessel (native coronary artery or bypass graft) OR B. Multivessel disease is present (visually-assessed angiographic DS ≥80% \[or ≥40% if non-invasive or invasive evidence of ischemia is present\] in ≥2 of the 3 epicardial coronary artery distributions in a main vessel or branch with visually-assessed reference vessel diameter ≥2.5 mm) and PCI is planned of at least 2 separate complex lesions in main vessels or branch vessels each having one or more of the following characteristics: i. Long lesion (≥28 mm visually assessed) requiring ≥30 mm stent length (single or multiple) ii. Severe angiographic calcification (see Protocol definition) or requiring atheroablation iii. Any left main morphology not in Criterion A requiring intervention (e.g., isolated ostial or mid-shaft left main lesion or distal left main bifurcation lesion with a planned single provisional stent technique) iv. Non-left main bifurcation lesion requiring intervention in both the main branch and side branch v. CTO (TIMI 0 Flow) vi. Giant thrombus (length ≥3x vessel diameter) vii. SVG (other than focal (\<5 mm) disease of the proximal or distal anastomosis or in-stent restenosis) NOTES:
• The multiple lesions can be in the same vessel if separated by ≥10 mm - however, each separate lesion has to have one or more of the above characteristics
• PCI may be performed on additional non-qualifying lesions (i.e., without 1 or more of the above high-risk characteristics) as long as there are at least two lesions also undergoing PCI with each having 1 or more of the above characteristics)
• There are 2 exceptions to the rule that each separate lesion must have one or more of the above characteristics (as in Inclusion Criterion 4B above): The subject may qualify if undergoing complex PCI of a single lesion that has 2 or more of the above complex characteristics (as in Inclusion Criterion 4B above) if also: i. There is a CTO of a proximal or mid-LAD, proximal or mid-LCX or proximal, mid- or distal RCA (i.e., not a branch vessel) that will not be treated OR ii. The subject qualifies with recent STEMI with an LVEF ≤30% and the complex PCI is planned in a non-infarct vessel (i.e., a complex PCI in the infarct vessel does not qualify)
• Subject or legal guardian (permitted at US sites only) agrees to randomization and to follow all study procedures and provides informed, written consent
Exclusion Criteria:
Subjects must not meet ANY of the following Exclusion Criteria to participate in the Trial:
• STEMI ≤24 hours from the onset of ischemic symptoms or at any time if mechanical complications of transmural infarction are present (e.g., VSD, papillary muscle rupture, etc.)
• Cardiogenic shock (SBP \<80 mmHg for ≥30 mins and not responsive to intravenous fluids or hemodynamic deterioration for any duration requiring pressors or mechanical circulatory support, including IABP)
• Subject is presently or recently intubated for the current admission (NOTE: recently intubated patients must be extubated for \>24 hours with full neurologic recovery)
• Cardiorespiratory arrest related to the current admission unless subject is extubated for \>24 hours with full neurologic recovery and hemodynamically stable
• Any contraindication or inability to Impella placement in both the left and right common femoral artery based on clinical or imaging findings, including iliofemoral artery diameter \<5 mm, tortuous vascular anatomy or severe bilateral peripheral vascular disease of the iliac or femoral arteries that can't be adequately treated (e.g., with intravascular lithotripsy) NOTES:
• Computed tomography (CT), magnetic resonance angiography (MRA) or contrast angiography to assess the aorta and iliofemoral vasculature to ensure Impella compatibility must be performed within 90 days prior to randomization. It is recommended that this evaluation be performed prior to the index procedure. Absent a qualifying pre-procedure imaging study, contrast angiography of the potential Impella access vessel(s) must be performed in the Cath Lab before the planned enrollment after which the subject may be randomized if he/she still qualifies. Of note, if pre-procedure imaging was performed and after this test but before randomization there was a worsening in PVD symptoms, repeat imaging must be performed prior to randomization.
• If iliofemoral peripheral vascular disease is present precluding Impella use that can be adequately treated with angioplasty, atherectomy or lithotripsy (without a stent), the subject can be enrolled if such treatment is undertaken and is successful and uncomplicated - randomization must not be performed until such successful and uncomplicated treatment
• Iliofemoral stents placed within 6 months of enrollment with planned vascular access through these vascular segments
• Vascular access for Impella is required in any location other than the left or right common femoral artery (i.e., axillary access, transcaval access, etc., for Impella access are not permitted)
• Known left ventricular thrombus
• Incessant ventricular arrhythmias that would likely preclude stable Impella positioning
• Severe aortic stenosis or severe aortic insufficiency
• Prior mechanical valve or self-expanding TAVR (NOTE: prior bioprosthetic surgical valve or balloon expandable TAVR implanted \>24 hours pre-procedure is acceptable)
• Prior CABG within three (3) months or successful prior PCI of at least one (1) attempted lesion within 12 months (including during the index hospitalization prior to randomization), that has not experienced stent thrombosis or restenosis during that 12-month period; the one (1) exception is that patients may be enrolled if a primary PCI for STEMI was performed during the index hospitalization without MCS and that was ≥24 hours and \<30 days prior to randomization. NOTE: Successful PCI for this exclusion criterion is defined as a visually-assessed angiographic DS ≤50% in at least one (1) attempted lesion.
• Prior placement of IABP, Impella or any other MCS device for any reason during the index admission, prior to randomization
• Known severe pulmonary hypertension (right ventricular systolic pressure (RVSP) on echo or pulmonary artery systolic pressure (PASP) on right heart catheterization) \>70 mm Hg unless active vasodilator therapy in the Cath Lab is able to reduce the pulmonary vascular resistance (PVR) to \<3 Wood Units or between 3 and 4.5 Wood Units with v-wave less than twice the mean of the pulmonary capillary wedge pressure
• Symptoms or signs of severe RV dysfunction, such as anasarca (NOTE: Leg edema alone does not necessarily indicate severe RV dysfunction if the investigator believes it is due to LV dysfunction)
• Severe tricuspid insufficiency
• Platelet count \<75,000 cells/mm3, bleeding diathesis or active bleeding, coagulopathy or unwilling to receive blood transfusions
• On dialysis
• Prior stroke with any permanent neurologic deficit within the previous three (3) months, or any prior intracranial hemorrhage or any prior subdural hematoma or known intracranial pathology pre-disposing to intracranial bleeding, such as an arteriovenous malformation or mass
• Taking a chronic oral anticoagulant that cannot be safely discontinued for at least 72-hours before and 72-hours after the index procedure (if a vitamin K antagonist) or that cannot be safely discontinued for at least 48 hours before and 48 hours after the index procedure (for a direct acting oral anticoagulant)
• Plan for any surgery within 6 months necessitating discontinuing antiplatelet agents
• Pregnant or child-bearing potential unless negative pregnancy test within 1 week
• Participation in the active treatment or follow-up phase of another clinical study of an investigational drug or device that has not reached its primary endpoint
• Any medical or psychiatric condition such as dementia, alcoholism or substance abuse which may preclude informed consent or interfere with any of the study procedures, including follow-up visits
• Any non-cardiac condition with life expectancy \<3 years (e.g., cirrhosis, oxygen or oral steroid dependent COPD, cancer not in remission, etc.)
• Subject is currently hospitalized for definite or suspected COVID-19
• Subject has previously been symptomatic with or hospitalized for COVID-19 unless he/she has been discharged (if hospitalized) and asymptomatic for ≥4 weeks and has returned to his/her prior baseline (pre-COVID) clinical condition
• Subject is asymptomatic (never ill) and COVID-19 PCR/antigen test is positive within the prior four (4) weeks unless a) subject remains asymptomatic for ≥2 weeks after the last positive test or b) the positive test occurred within six (6) months after the subject received a COVID vaccine
• Subject belongs to a vulnerable population (defined as individuals with mental disability, impoverished persons, homeless persons, nomads, refugees and those permanently incapable of giving informed consent; vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces and persons kept in detention)
DEVICE: Impella CP® / Impella CP® with SmartAssist® / Impella 2.5®, DEVICE: IABP Intra-aortic balloon pump
Left Ventricular Dysfunction, Coronary Artery Disease
Non-ST Elevated Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Myocardial Ischemia, Myocardial Infarction, Anterior Wall Myocardial Infarction, Inferior Wall Myocardial Infarction
Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery (ASTER)
Katie Oldmixon, RN - coldmixon@mgh.harvard.edu
Fowler, Alpha, A
NCT04291508
HM20023257
Inclusion Criteria:
• Age ≥ 18 years
• Sepsis defined as:
• Clinical evidence of a known or suspected infection and orders written to administer antibiotics AND
• Hypotension as defined by the need for any vasopressor (and 1 liter of fluid already administered intravenously for resuscitation) OR respiratory failure defined by mechanical ventilation, BIPAP or CPAP at any level, or greater than or equal to 6 liters/minute of supplemental oxygen (criterion b must be met at time of enrollment)
• Admitted to a study site ICU (or intent for the patient to be admitted to a study site ICU) within 36 hours of presentation to the ED or admitted to the study site ICU within 36 hours of presentation to any acute care hospital
Exclusion Criteria:
• No consent/inability to obtain consent from the participant or a legally authorized representative
• Patient unable to be randomized within 36 hours of presentation to the ED or within 36 hours of presentation to any acute care hospital
• Diagnosis of cirrhosis by medical chart review
• Liver transplant recipient
• AST or ALT greater than five times upper limit of normal
• Diagnosis of ongoing chronic alcohol use disorder/abuse by chart review; if medical record unclear, use Appendix F
• Clinical diagnosis of diabetic ketoacidosis or other condition such as profound hypoglycemia that requires hourly blood glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Hypersensitivity to Acetaminophen or Vitamin C
• Patient, surrogate or physician not committed to full support (Exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
• Home assisted ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing
• Chronic dialysis
• Current active kidney stone (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Multiple (>1) episodes of prior kidney stones, known history of oxalate kidney stones, or history of oxalate nephropathy. (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Kidney transplant recipient (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
• Use of home oxygen >3L/minute via nasal cannula for chronic cardiopulmonary disease
• Moribund patient not expected to survive 24 hours
• Underlying malignancy or other condition with estimated life expectancy of less than 1 month
• Pregnant woman, woman of childbearing potential without a documented negative urine or serum pregnancy test during the current hospitalization, or woman who is breast feeding
• Prisoner
• Treating team unwilling to enroll because of intended use of Acetaminophen or Vitamin C
• Treating team unwilling to use plasma (as opposed to point of care testing) for glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial).
Drug: Intravenous Acetaminophen (room temperature), Drug: Intravenous Vitamin C (refrigerated), Drug: 5% Dextrose (room temperature), Drug: 5% Dextrose refrigerated
Acute Respiratory Distress Syndrome, Critical Illness, Respiratory Failure, Sepsis
ARDS, Acetaminophen, Vitamin C, Sepsis
Trifecta-Kidney cfDNA-MMDx Study
Konrad S Famulski, PhD - konrad@ualberta.ca
NCT04239703
Inclusion Criteria:
* All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.
Exclusion Criteria:
* Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients. DIAGNOSTIC_TEST: MMDx, DIAGNOSTIC_TEST: Prospera, DIAGNOSTIC_TEST: HLA antibody
Kidney Transplant Rejection
donor derived cell-free DNA, blood, kidney biopsy
Long-Term Follow-Up of Patients Who Have Participated in Children's Oncology Group Studies
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Gowda, Madhu, S
NCT00736749
HM12659
Inclusion Criteria:
* The patient must reside in the U.S. on the date of enrollment to ALTE05N1
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Assessment of Therapy Complications, OTHER: Questionnaire Administration
Hematopoietic Cell Transplantation Recipient, Leukemia, Solid Tumor
Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial (INNOVATE)
Loney, Shenise - loneys2@vcu.edu
Urdaneta, Alfredo, I
NCT04134260
HM20021914
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
* Any T-stage is eligible (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed\])
* Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA \< 0.20 ng/mL at time of registration, PET scan is recommended but not required
* Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
* History/physical examination within 90 days prior to registration
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
* Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA \> 0 ng/mL at least 30 days after prostatectomy
* Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =\< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =\< 180 days and stopped prior to registration)
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
* Serum potassium \>= 3.5 mmol/L within 90 days prior to registration
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 90 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 90 days prior to registration)
* Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for \< 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, \[FACBC, Axumin\], F-18 PSMA PET \[Pylarify\], flotufolastat F-18 PSMA PET scan \[Posluma\], Gallium-68 PSMA PET scan or C-11 choline PET)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Androgen deprivation therapy (ADT) prior to radical prostatectomy
* Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =\< 180 days and stopped prior to registration, which is allowed
* Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:
* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
* Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
* New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.)
* History of any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:
* Known gastrointestinal disorder affecting absorption of oral medications
* Active uncontrolled infection
* Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
* Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
* Baseline moderate and severe hepatic impairment (Child-Pugh Class B \& C)
* Inability to swallow oral pills
* Any current condition that in the opinion of the investigator, would preclude participation in this study
* Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
* Patients with inflammatory bowel disease DRUG: Apalutamide, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Hormone Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy
Prostate Adenocarcinoma, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8
Prostate Cancer, Apalutamide, Abiraterone Acetate
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF (Rebalance-HF) (Rebalance-HF)
Sears, Melissa, L - melissa.sears@vcuhealth.org
Shah, Keyur, B
NCT04592445
HM20022228
Inclusion Criteria:
• Subjects ? 40 years of age
• Chronic heart failure defined as at least one of the following:
• Symptoms of HF requiring current treatment with diuretics (intermittent or continuous) for > 30 days, AND
• NYHA class II with a history of > NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening; or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
• > 1 HF hospital admission (with HF as the primary, or secondary diagnosis);
• OR - treatment with intravenous (IV) diuretics, or intensification of oral diuresis for HF in a healthcare facility within the 12 months prior to study entry;
• OR - NT-pro BNP value > 150 pg/ml in normal sinus rhythm, > 450 pg/ml in atrial fibrillation within the past 6 months;
• OR - BNP value > 50 pg/ml in normal sinus rhythm, > 150 pg/ml in atrial fibrillation within the past 6 months.
• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2017 ACCF/AHA Guideline for the Management of Heart Failure, with no significant changes [>100% increase or 50% decrease] for a minimum of 1 month prior to screening, that is expected to be maintained without change for at least 3 months.
• LVEF ? 50 % (site determined by TTE) in the past 3 months.
• Site determined elevated PCWP documented by right heart catheterization by PCWP ? 25 mmHg during supine ergometer exercise a. PCWP to be evaluated by a Swan Ganz procedure performed either prior to the day of the index procedure or on the day of the index procedure
• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
Exclusion Criteria:
• MI (type I) and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization.
• Cardiac Resynchronization Therapy initiated within the past 3 months prior to screening.
• Advanced heart failure defined as one or more of the below:
• ACC/AHA/ESC Stage D heart failure, non-ambulatory NYHA Class IV HF
• Cardiac index < 2.0 L/min/m2
• Inotropic infusion (continuous or intermittent) for LV EF< 30% within the past 6 months prior to screening
• Subject is on the cardiac transplant waiting list
• BMI > 45 kg/m2
• Inability to perform 6-minute walk test (distance < 100 meters), OR ability to perform 6-minute walk test distance > 450 meters.
• Admission for HF within the 30 days prior to planned index procedure.
• In the last 3 years an ejection fraction (EF) below 40
• Systolic BP < 100 mmHg or > 170 mmHg despite appropriate medical management.
• Symptomatic orthostatic hypotension or orthostatic hypotension requiring treatment (orthostatic hypotension is defined as systolic blood pressure decrease of >20mmHg and/or increase in heart rate >20 bpm upon going from supine to standing position).
• Arterial oxygen saturation < 90 % on room air.
• Presence of significant valve disease defined by the site cardiologist as:
• Mitral valve stenosis defined as <1.5 cm2 (or greater than mild)
• Mitral valve regurgitation defined as grade > 3+ MR
• Tricuspid valve regurgitation defined as grade > 3+ TR
• Aortic valve disease defined as > 3+ AR or > severe AS
• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis)
• Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.
• Mean resting right atrial pressure (RAP) > 20 mmHg based upon screening right heart catheterization.
• History of severe liver cirrhosis
• Dialysis dependent; or estimated-GFR <25 ml/min/1.73 m2 by MDRD equation.
• Baseline status of persistent atrial fibrillation with resting HR >100 beats per minute that could obfuscate RHC interpretation.
• Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation (including intubations) in the 12 months before study entry OR known history of GOLD Class II or higher COPD.
• Currently participating in conflicting investigational drug or device study.
• Life expectancy <12 months for non-cardiovascular reasons.
• Any condition, or history of illness or surgery that, in the opinion of the Investigator, might confound the results of the study or pose additional risks to the patient.
• Females who are not pregnant or lactating and not or planning to become pregnant for the duration of the study during the next year.
Device: Satera GSN Ablation, Device: Sham Control
Heart Failure With Preserved Ejection Fraction, Diseases of Circulatory System (390-459)
Therapeutic Hepatitis C Virus Vaccine
Smith, Paula - paula.smith@vcuhealth.org
Sterling, Richard, K
NCT04318379
HM20021916
Inclusion Criteria:
• Documentation of chronic hepatitis C infection based on serum positivity for HCV RNA for at least 6 months interval. HCV genotype will be recorded. All genotypes will be eligible.
• Patients who are not under DAA treatment.
• Liver fibrosis (by Metavir stage F1 or F0) within one year of the screening visit, documenting extent of liver disease consistent with chronic hepatitis C with evidence of inflammation and/or fibrosis. Fibrosis scaling is based on an ultrasound based elastography (FibroScan, Echosen, Paris France) with cutoff of 7.5 kPa or liver biopsy.
• Screening laboratory values within institutional normal range, with the exception of liver enzymes ? 3 ULN and bilirubin <1.5 ULN, or judged to be not clinically significant by clinical investigator.
• Ability and willingness of subject to give written informed consent.
• Negative pregnancy test on the day prior to each vaccination.
• Willingness to use adequate contraception by study participants. Subjects must agree not to participate in a conception process (e.g., active attempts to become pregnant or to impregnate, sperm donation, or in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, subjects must use a form of contraception as listed below while on study vaccine and for 60 days after stopping study vaccine. Women without reproductive potential (i.e., have reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) or women whose male partner has undergone successful vasectomy with documented azoospermia or has documented azoospermia for any other reason, are eligible without requiring the use of contraception.
Exclusion Criteria:
• History of decompensated liver disease, including but not restricted to, portal hypertension as manifested by a known history of gastroesophageal varices, variceal bleeding, ascites or encephalopathy, histopathologic or clinical evidence of cirrhosis, hepatocellular carcinoma, or renal impairment consistent with hepatorenal syndrome; history of significant other non-HCV chronic liver disease, i.e. alcoholic hepatitis, autoimmune hepatitis.
• History of hematologic disease (e.g., cryoglobulinemia, lymphoma), renal disease, dermatologic disease (e.g., lichen planus, porphyria cutanea tarda).
• Seropositive for hepatitis B surface antigen (HBsAg) or HIV-1 antibody.
• Autoimmune diseases or clinically serious cardiac, pulmonary, gastrointestinal, hepatic, renal or neurologic disease, which in the opinion of the investigator will compromise ability to participate in the study.
• Previous receipt of any HCV experimental vaccine.
• Pregnancy and breast-feeding.
• Prior or current systemic cancer chemotherapy.
• Investigational agents and immunomodulators (cyclosporine, hematological growth factors, systemic corticosteroids, interleukins or interferons) within 90 days prior to study entry. NOTE: Subjects may not be on antiretroviral agents not yet approved by the FDA as part of a clinical trial or expanded access program.
• Anaphylaxis or allergy to vaccine components.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Any other serious diseases other than HCV infection including current or recent (within 5 years) cancers.
• Liver fibrosis with Metavir stage F2 or above.
• Subjects with diabetes mellitus, who are at higher risk for more rapid progression of fibrosis.
• Subjects who are immunocompromised or immunosuppressed due to disease or medications.
• Subjects with any laboratory abnormalities Grade 3 or greater.
• Women who are lactating.
Biological: HCVax,
drug: Hcvax?
Chronic Hepatitis C Infection, Infectious and Parasitic Diseases (001-139)
Therapeutic HCV vaccine, HCV
Preventing Firearm Violence in Youth: A Hospital-based Prevention Strategy
Nicholas Thomson - Nicholas.Thomson@vcuhealth.org
Thomson, Nicholas
NCT05078164
HM20022975
Inclusion Criteria:
• Youth are aged 10-17 years and their adult caregivers are aged 18 years and older
• Receiving treatment in the hospital for a violence-related injury (e.g., gunshot wound) or referred to BTG/IVPP services
• English speaking
• Eligible for BTG services (which includes living within the BTG catchment area for the hospital; Richmond City and neighboring counties)
Exclusion Criteria:
• Youth are \< 10 years old
• Youth are \> 18 years old
• Prisoners
BEHAVIORAL: Bridging the Gap (BTG)
Violence in Adolescence
A Study to Learn About How Well Riociguat Works, How Safe it is and How it is Used Under Real World Conditions in Patients in the United States Who Are Receiving Riociguat for High Blood Pressure in the Arteries That Carry Blood From the Heart to the Lungs (Pulmonary Arterial Hypertension, PAH) (ROAR)
Bayer Clinical Trials Contact - clinical-trials-contact@bayer.com
Grinnan, Daniel, C
NCT04813926
HM20022707
Inclusion Criteria:
• Patients aged ≥18 years at the time of riociguat treatment initiation
• Diagnosis of PAH per National Institute for Health and Care Excellence (NICE) 2018 classification
• Decision to initiate treatment with riociguat as per investigator's routine treatment practice made prior to enrollment in the study
• Initiation of riociguat, as per the FDA-approved US label:
• At enrollment OR
• ≤90 days prior to enrollment, with a documented titration regimen (defined as all documented dose changes including, but not limited to: starting dose and dates and highest tolerated dose and dates)
• Signed informed consent
Exclusion Criteria:
• Previously treated with and discontinued use of riociguat for any reason prior to study enrollment (discontinuation defined as an interruption of therapy ≥30 days)
• Participating in any of the following:
• Blinded clinical trial
• Clinical trial involving an unapproved drug
• Investigational program with interventions outside of routine clinical practice
• Life expectancy <12 months
• Contraindicated to receive riociguat per the FDA approved US label
• Use of nitrates or NO donors in any form
• Use of PDE5 inhibitors
• PH associated with idiopathic interstitial pneumonias
• Unable or unwilling to provide informed consent
Drug: Riociguat (Adempas, BAY63-2521)
Pulmonary Arterial Hypertension
A Pilot Study to Examine the Impact of a Therapy Dog Intervention on Loneliness and Related Health Outcomes in Vulnerable Populations
Nancy R. Gee, PhD - Nancy.Gee@vcuhealth.org
Gee, Nancy
NCT05089201
HM20021567
Inclusion Criteria:
• 18 years of age or older
• Projected to be admitted to the hospital for the upcoming four days
• Speak English
• Able to provide consent.
Exclusion Criteria:
• Fear of, or allergy to, dogs
• Documented contact precautions
• Cognitive impairment that prevents consent or completion of measures.
Behavioral: Animal-assisted interaction, Behavioral: Conversational control
Loneliness, Depression, Anxiety, Quality of Life
Evaluation of Dosing Procedures of Chemotherapy Treatment (Carboplatin) With the Contrast Agent Iohexol
Washington, Sonya, L - slwashington@vcu.edu
Randall, Leslie
NCT03997370
HM20020535
Inclusion Criteria:
* Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
* For men who are sexually active, the need for use of medically acceptable contraception will be dictated by the primary treatment plan/protocol
* Study accrual was closed to women on 08/18/2021 and accrual is now only open to males in order to meet accrual goals and study objectives. (11-AUG-2021)
* Male sex
* Any patients who will receive treatment with intravenous carboplatin (any AUC, any cycle) on a National Cancer Institute (NCI)-sponsored National Clinical Trial Network (NCTN)-, Experimental Therapeutics Clinical Trials Network (ETCTN)-, trial, local trial, or through standard of care
* Age \>= 18
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Treated at an institute where creatinine is not measured with an IDMS calibrated assay
* History of allergic reactions to computed tomography (CT) contrast, iodine or shellfish, or history of anaphylactic reaction to any food item
* Recent (last 6 months) episode of acute kidney injury, have sickle cell disease, or have current indwelling nephrostomy tubes
* Edema beyond trace edema, because this will impact iohexol equilibration and distribution
* Ascites (including pleural effusion) beyond trace ascites, because this will impact iohexol equilibration and distribution
* Whole- or part-limb amputees, because this will impact iohexol equilibration and distribution
* Inability to maintain a constant dose and schedule of anti-inflammatory agents, diuretics, angiotensin II receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEi) for one week prior to study visit, as this impacts renal function. If the patient is on a nonsteroidal anti-inflammatory drug (NSAID), diuretic, ARB or ACEi, they are eligible as long as these agents are taken on a set schedule for 7 or more days prior to study (and not on an "as needed" basis as that can cause fluctuations in renal function)
* Inadequate venous access to obtain pharmacokinetic (PK) specimens
* Multinodular goiter, Graves' disease or autoimmune thyroiditis, per iohexol package insert (hypothyroidism is allowed) PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Iohexol
Malignant Solid Neoplasm
Phase 3 Study of MRTX849 +Cetuximab vs Chemo in Patients W/ Advanced Colorectal Cancer w/ KRAS G12C
Donovan, Carrie - cdonovan2@vcu.edu
Matin, Khalid
NCT04793958
HM20022574
Inclusion Criteria:
• Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue.
• Prior receipt of 1st line treatment in advanced CRC with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan, and radiographically documented progression of disease on or after treatment.
Exclusion Criteria:
• Prior treatment with a therapy targeting KRAS G12C mutation (e.g., AMG 510).
• Prior treatment with an anti-EGFR antibody (e.g., cetuximab or panitumumab).
• Active brain metastasis
Drug: MRTX849, Biological: Cetuximab, Drug: mFOLFOX6 Regimen, Drug: FOLFIRI Regimen,
drug: Mrtx849,
drug: Leucovorin,
drug: Folinic acid,
drug: Cetuximab,
drug: 5-fluorouracil
Advanced Colorectal Cancer, Metastatic Colorectal Cancer, Rectum, Colon
Colorectal Cancer, Colorectal Cancer Trial, Colorectal Carcinoma, Rectal Cancer, Colon Cancer, KRAS, KRAS G12C, RAS, Colorectal Adenocarcinoma
Novel Experimental COVID-19 Therapies Affecting Host Response (NECTAR)
Sheri L. Dixon, B.S.N., R.N. - sheri.dixon@vumc.org
de Wit, Marjolein
NCT04924660
HM20022625
Inclusion criteria
• Hospitalized for COVID-19
• ≥18 years of age
• SARS-CoV-2 infection, documented by:
• a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
• documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
• Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
• Symptoms or signs of acute COVID-19, defined as one or more of the following:
• cough
• reported or documented body temperature of 100.4 degrees Fahrenheit or greater
• shortness of breath
• chest pain
• infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) Exclusion criteria
• Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
• Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
• Pregnancy
• Breastfeeding
• Prisoners
• End-stage renal disease (ESRD) on dialysis
• Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life.
• The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
• Known allergy/hypersensitivity to IMP or its excipients The following exclusion criteria differ from the master protocol criteria: TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual):
• Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual):
• Participants on ARBs will be excluded from this study arm.
• Patient unable to participate or declines participation in the TRV027 arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days Fostamatinib specific exclusion criteria: The following exclusion criteria differ from the master protocol criteria:
• Randomized in another trial evaluating fostamatinib in the prior 30 days Study arm exclusion criteria measured within 24 hours prior to randomization:
• AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
• SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
• ANC < 1000/mL
• Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
• Patient unable to participate or declines participation in the fostamatinib arm.
• Hospitalized for COVID-19
• ≥18 years of age
• SARS-CoV-2 infection, documented by:
• a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR
• documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non- NAT tests is maintained in Appendix E. Appendix E. Non-NAT Tests Deemed with Equivalent Specificity to NAT by the Protocol Team).
• Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy
• Symptoms or signs of acute COVID-19, defined as one or more of the following:
• cough
• reported or documented body temperature of 100.4 degrees Fahrenheit or greater
• shortness of breath
• chest pain
• infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) Exclusion criteria
• Onset of COVID-19 symptom fulfilling inclusion criterion #5 >14 days prior to randomization
• Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission)
• Pregnancy
• Breastfeeding
• Prisoners
• End-stage renal disease (ESRD) on dialysis
• Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life.
• The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient
• Known allergy/hypersensitivity to IMP or its excipients The following exclusion criteria differ from the master protocol criteria: TXA127-specific exclusion criteria(4/20/2022 Closed to Accrual):
• Patient unable to participate or declines participation in the TXA127/Ang(1-7) arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days TRV027-specific exclusion criteria (4/20/2022 Closed to Accrual):
• Participants on ARBs will be excluded from this study arm.
• Patient unable to participate or declines participation in the TRV027 arm.
• History of sensitivity (including angioedema) or allergic reaction to medication targeting the RAAS system including study medications or other allergy in the opinion of the investigator that contraindicates participation (not applicable to fostamatinib arm)
• Hemodynamic instability - defined as MAP < 65 mmHg at time of randomization confirmed on two measurements 5 minutes apart OR vasopressors at or above norepinephrine equivalent of 0.1 mcg/kg/min in prior 4 hours to maintain MAP > 65 mmHg.
• Known severe renal artery stenosis.
• Known significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic or mitral stenosis.
• Randomized in another trial evaluating RAAS modulation in the prior 30 days Fostamatinib specific exclusion criteria: The following exclusion criteria differ from the master protocol criteria:
• Randomized in another trial evaluating fostamatinib in the prior 30 days Study arm exclusion criteria measured within 24 hours prior to randomization:
• AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN
• SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization
• ANC < 1000/mL
• Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib,Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx.
• Patient unable to participate or declines participation in the fostamatinib arm.
Drug: TXA127, Drug: TRV027, Drug: Placebo, Drug: Fostamatinib
COVID-19, SARS-CoV-2 Infection, Coronavirus Infection
COVID-19 drug treatment, RAAS
CONTIGO - A Narrative Intervention to Enhance Genetic Counseling and Testing
Alejandra Hurtado de Mendoza, Ph.D - ahd28@georgetown.edu
NCT05130606
Inclusion Criteria:
Aim 1 and 2.
* Self-identify as a Latina woman
* Be 18 years old or older
* Be able to provide informed consent
* Be fluent in Spanish
* Meet NCCN criteria to be considered for genetic cancer risk assessment for HBOC, whether by a personal history of cancer or family history of cancer
* No previous participation in genetic counseling or testing for hereditary breast and ovarian cancer risk
* No other family members are participating in this study
* Have not participated in any previous studies involving interventions about HBOC or GCT
Aim 3.
* Be 18 years old or older
* Be fluent in English or Spanish
* Have a role in the partner community clinic as either a) full-time or part-time employee b) intern c) volunteer
Exclusion Criteria:
\- BEHAVIORAL: Culturally Targeted Narrative Video: "Is My Cancer Hereditary? Rosa Visits a Genetic Counselor.", BEHAVIORAL: FORCE Fact Sheet
Hereditary Breast and Ovarian Cancer
Breast cancer, Ovarian cancer, Hereditary cancer, Latinas
Eliminating Monitor Overuse Trial (EMO Trial) (EMO Trial)
Christopher P Bonafide, MD, MSCE - bonafide@chop.edu
Lee, Clifton, C
NCT05132322
HM20022900
Population 1a: Hospital staff who complete study questionnaires.
Inclusion Criteria:
* Nurse or physician fluent in English and employed full-time by the hospital, affiliated practice, or affiliated university who cared for bronchiolitis patients on a unit participating in the trial during at least 5 days of the most recent bronchiolitis season
* Hospital administrator fluent in English who oversaw the care of bronchiolitis on a local level (e.g. nurse manager) or a hospital level (e.g. Chief Quality and Safety Officer)
Exclusion Criteria:
• Under the direct supervision of study or site principal investigator(s)
Population 1b: Hospital staff who participate in qualitative interviews
In Aim 2, we will conduct semi-structured interviews with physicians and nurses who provide care to bronchiolitis patients in participating units at the 5 hospitals with the highest and 3 hospitals with the lowest sustainability (8 hospitals total; up to maximum of 8 interviews/hospital). Maximum anticipated enrollment 64.
Inclusion criteria:
* Nurses or Physicians who cared for bronchiolitis patients on a unit participating in the trial during at least 5 days of the most recent bronchiolitis season
* Employed full-time by the hospital, affiliated practice, or affiliated university
* Fluent in English
Exclusion criteria:
• No exclusion criteria
Population 2a: Bronchiolitis patients directly observed while not receiving supplemental oxygen ("in room air," for primary trial outcome)
Inclusion Criteria:
* Infants and children 2 months through 23 months old
* Hospitalized on non-ICU wards participating in the trial
* Cared for by generalist inpatient services (e.g. general pediatrics, hospital medicine)
* Primary diagnosis of bronchiolitis in most recent physician progress note
* Not actively receiving supplemental oxygen ("in room air")
* Last documented receipt of supplemental oxygen \>1 hour prior to direct observational data collection
Exclusion Criteria:
* Documented apnea or cyanosis during the current illness
* Extreme prematurity (\<28 weeks completed gestation)
* Cardiac disease
* Pulmonary hypertension
* Chronic lung disease
* Home oxygen requirement
* Neuromuscular disease
* Immunodeficiency
* Cancer
* Severe Acute Respiratory Syndrome Coronavirus 2 (Covid-19 / SARS-CoV-2)-related illness (known or suspected, including multisystem inflammatory syndrome in children multi-system inflammatory syndrome in children (MIS-C)
Population 2b: Bronchiolitis patients directly observed while receiving supplemental oxygen (for underuse evaluation).
Inclusion Criteria:
* Infants and children 2 months through 23 months old
* Hospitalized on non-ICU wards participating in the trial
* Cared for by generalist inpatient services (e.g. general pediatrics, hospital medicine)
* Primary diagnosis of bronchiolitis in most recent physician progress note
* Actively receiving ≥2 Liters/minute (2L/min) supplemental oxygen or 21% room air flow
Exclusion Criteria:
* Extreme prematurity (\<28 weeks completed gestation)
* Cardiac disease
* Pulmonary hypertension
* Chronic lung disease
* Home oxygen requirement
* Neuromuscular disease
* Immunodeficiency
* Cancer
* Severe Acute Respiratory Syndrome Coronavirus 2 \[Covid-19 / SARS-CoV-2 (known or suspected)\]
Population 3: Parents or guardians of bronchiolitis patients who participate in qualitative interviews.
Inclusion Criteria:
* Their child was hospitalized for bronchiolitis on a unit participating in the trial during the most recent bronchiolitis season
* Their child was found to be in room air during Aim 1 data collection
* Fluent in English
Exclusion criteria:
• They are an employee of the hospital or a hospital volunteer BEHAVIORAL: Educational Outreach, BEHAVIORAL: Audit & Feedback (unit level), BEHAVIORAL: Audit & Feedback (real time, individual-level), BEHAVIORAL: Clinical Pathway Integrated into Electronic Health Record
Bronchiolitis Acute Viral
pulse oximetry, deimplementation, cluster-randomized trial, effectiveness-implementation hybrid trial, implementation science
S1827 (MAVERICK) Testing Whether the Use of Brain Scans Alone Instead of Brain Scans Plus Preventive Brain Radiation Affects Lifespan in Patients With Small Cell Lung Cancer (MAVERICK)
Hamilton, Melanie, R - mrhamilton2@vcu.edu
Weiss, Elisabeth
NCT04155034
HM20021863
Inclusion Criteria:
* Patient must have a histologically confirmed diagnosis of small-cell lung cancer (SCLC)
* Patient must have an MRI of the brain performed within 28 days prior to registration documenting no evidence of brain metastases or leptomeningeal disease. Patient also must not have a history of brain metastases or leptomeningeal disease
* Immunotherapy concurrent with and/or adjuvant to first-line therapy is allowed at the discretion of the treating physician. Patients with limited-stage (LS)-SCLC must have completed platinum-based chemotherapy and either definitive thoracic radiotherapy (including stereotactic body radiation therapy \[SBRT\] for early-stage T1-2 N0 M0 disease who do not undergo surgery) or definitive surgical resection; thoracic radiation in addition to definitive surgical resection is allowed at the discretion of the treating physician, but is not required. Patients with extensive-stage (ES)-SCLC must have completed platinum-based chemotherapy either with or without thoracic radiotherapy at the discretion of the treating physician
* All adverse events from prior treatment must have resolved to =\< grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) prior to randomization
* Patient must have had a response to first-line therapy and no evidence of progression in opinion of the treating investigator. Systemic imaging (computed tomography \[CT\] or positron emission tomography \[PET\]/CT including the chest and abdomen) must be performed within 28 days prior to randomization
* No more than 8 weeks may have elapsed between day 1 of the last cycle of chemotherapy and randomization
* Patient must not have received prior radiotherapy to the brain or whole brain radiotherapy. Patients who have undergone prior stereotactic radiosurgery for benign tumors or conditions (e.g., acoustic neuroma, grade I meningioma, trigeminal neuralgia) may be considered on a case-by-case basis
* Patient must have Zubrod performance status of 0-2
* Patient must not have a contraindication to MR imaging, such as implanted metal devices or foreign bodies
* Patient must not have a contraindication to gadolinium contrast administration during MR imaging, such as allergy or insufficient renal function
* Patient must not have other metastatic malignancies requiring current active treatment
* Patient must not have any severe active comorbidities, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to randomization
* Transmural myocardial infarction within 6 months prior to randomization
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
* Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of randomization
* Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
* Human immunodeficiency virus (HIV) positive with CD4 count \< 200 cells/microliter
* Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 16 weeks prior to randomization
* Note also that HIV testing is not required for eligibility for this protocol
* Patient must not be pregnant because of fetal risks from radiation exposure. Men must have agreed to use an effective contraceptive method during PCI and for six months after completing PCI. Women of reproductive potential must have agreed to use an effective contraceptive method during PCI. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Patients who speak and understand English or French must agree to participate in cognitive function testing
* Patient must be offered the opportunity to have specimens submitted for banking
* Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
* As a part of the Oncology Patient Enrollment Network (OPEN) randomization process the treating institution?s identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system PROCEDURE: Magnetic Resonance Imaging, RADIATION: Prophylactic Cranial Irradiation
Extensive Stage Lung Small Cell Carcinoma, Limited Stage Lung Small Cell Carcinoma, Lung Small Cell Carcinoma
MYTHS - MYocarditis THerapy With Steroids (MYTHS)
Enrico Ammirati, MD, PhD - enrico.ammirati@ospedaleniguarda.it
NCT05150704
Inclusion Criteria:
* Patients admitted to hospital for suspected AM
* Age 18 years or older and below 70 years (18-69 years)
* Acute HF with clinically suspected acute myocarditis based on an N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration of 1600 pg/mL or more or a B-type natriuretic peptide (BNP) concentration of 400 pg/mL or more;
* Left ventricular ejection fraction (LVEF)\<41% and left ventricular end diastolic diameter (LV-EDD)\<56 mm (parasternal long-axis view) on echocardiogram;
* Increased troponin (3x upper reference limit \[URL\]) at the time of randomization;
* Clinical onset of cardiac symptoms within 3 weeks from randomization;
* Excluded coronary artery disease by coronary angiogram in subjects ≥46 years of age, in case myocarditis is not histologically proven;
* Randomization within 120 hours from hospital admission.
Exclusion Criteria:
* Known systemic autoimmune disorder or other conditions at the time of randomization where immunosuppression is assumed useful. Patients in whom a systemic autoimmune disorder will be diagnosed during hospitalization will be included in the study if randomized, including patients with a diagnosis of cardiac sarcoidosis or giant cell myocarditis (GCM). Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis of a systemic autoimmune disorder, or cardiac sarcoidosis or GCM;
* Patients already on oral/IV chronic corticosteroid therapy or other chronic immunosuppressive therapies (colchicine or nonsteroidal anti-inflammatory drugs \[NSAIDs\] are not considered immunosuppressive drugs);
* Contraindication to corticosteroids, including allergies to this medication and its excipients;
* Patients with persistent peripheral eosinophilia (persistent Eosinophil count \>7% of the leukocytes) or known hypereosinophilic syndrome at the time of randomization. Patients in whom eosinophilic myocarditis will be diagnosed on endomyocardial biopsy (EMB) will be included in the study if already randomized. Both patients included in the corticosteroids-treatment arm or in the placebo-treatment arm can receive the standard immunosuppressive therapy used in the center since the diagnosis;
* Myocarditis associated with the ongoing administration of anti-cancer immune checkpoint inhibitor (ICI) agents;
* Previously known chronic cardiac disease (i.e., previous cardiomyopathy) that does NOT include previous myocarditis if there is a functional recovery at the time of screening);
* Evidence of active bacterial or fungal infectious disease (presence of fever or increased C-reactive protein are not considered exclusion criteria), or suspected bacterial/fungal infection associated with increased levels of procalcitonin (cut-off \>10 ng/mL), if the laboratory exam is available in the center;
* Known chronic infective disease, such as HIV infection or tuberculosis;
* out-of-hospital cardiac arrest;
* t-MCS instituted more than 48 hours before randomization;
* Patients clinically judged too sick to initiate t-MCS (i.e., irreversible multiorgan failure);
* Echocardiographic presence of images suggestive of other cardiac diseases (i.e. endocarditis)
* Participants involved in another clinical trial;
* Pregnant women (known pregnancy) or POSITIVE human chorionic gonadotropin (HCG) test measures (urine/blood) for women of 18-50 years of age.
* Any other significant disease with expected life expectancy \<12 months (i.e., evidence of irreversible severe brain injury) or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. DRUG: Methylprednisolone, DRUG: saline solution
Myocarditis Acute
Acute Myocarditis, Corticosteroid therapy, Myocarditis, Trial, Immunosuppression, Acute heart failure, Fulminant acute myocarditis
Safety, Tolerability, and Efficacy of AXA1125 in NASH With Fibrosis (EMMPACT)
Margaret Koziel, MD - clinicaltrials@axcellahealth.com
Siddiqui, Mohammad, S
NCT04880187
HM20022234
Inclusion Criteria:
• Willing to participate in the study and provide written informed consent.
• Male and female adults aged > 18 years.
• Must have NASH and fibrosis on a liver biopsy sample
• If a historical liver biopsy is used for Screening, obtained within 6 months prior to Screening;
• Subjects may have a diagnosis of T2DM
Exclusion Criteria:
• History or presence of liver disease (other than NAFLD or NASH)
• History or presence of cirrhosis and/or history or presence of hepatic decompensation
Drug: AXA1125, Drug: Placebo
Non Alcoholic Steatohepatitis (NASH)
Steatosis, Lobular inflammation, Ballooning, Liver biopsy, Liver fat, Liver stiffness, NASH, Aminio Acids, Fibrosis
A Study to Evaluate Safety and Efficacy of Selinexor Versus Treatment of Physician's Choice in Participants With Previously Treated Myelofibrosis
Karyopharm Medical Information - clinicaltrials@karyopharm.com
Maher, Keri
NCT04562870
HM20022272
Inclusion Criteria:
• A diagnosis of primary MF or post-essential thrombocythemia (ET) or post-polycythemia (PV) MF according to the 2016 World Health Organization (WHO) classification of myeloproliferative neoplasms (MPN), confirmed by the most recent local pathology report.
• Previous treatment with JAK inhibitors for at least 6 months.
• Measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥450 centimeter cube (cm^3) by magnetic resonance imaging (MRI) or computerized tomography (CT) scan.
• Relapsed, Refractory or Intolerant to JAK inhibitors as defined as meeting one of the criteria below:
• less than (<) 35% spleen volume reduction by MRI or CT-scan (from baseline) or
• <50% decrease in spleen size by palpation (from baseline) or an increase of at least 3 cm with the spleen at least 5 cm below the left costal margin or
• Spleen volume increase greater than (>) 25% from nadir or a return to within 10% of baseline after any initial response or
• Treatment with JAK inhibitor was complicated by development of red blood cells (RBC) transfusion requirement (2 units per month for 2 month); or grade 3 thrombocytopenia, anemia, hematoma/hemorrhage; or grade 2 non-hematologic toxicity while on JAK inhibitors
• Participants ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤) 2.
• Platelet count ≥75*10^9 per liter (/L).
• Absolute neutrophil count (ANC) ≥1.5*10^9/L.
• Serum direct bilirubin ≤1.5*upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5*ULN.
• Calculated creatinine clearance (CrCl) >15 milliliter (mL)/minute (min) based on the Cockcroft and Gault formula.
• Participants with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International Units (IU)/mL.
• Participants with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
• Participants with history of human immunodeficiency virus (HIV) are eligible if they have cluster of differentiation 4 (CD4)+ T-cell counts ≥350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
• Female participants of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
• Male participants who are sexually active must use highly effective methods of contraception throughout the study and for at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). Male participants must agree not to donate sperm during the study treatment period.
• Participants must sign written informed consent in accordance with federal, local and institutional guidelines.
Exclusion Criteria:
• >5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase).
• Previous treatment with selinexor or other exportin 1 (XPO1) inhibitors.
• Use of any standard or experimental anti-MF therapy <21 days prior to Cycle 1 Day 1 (hydroxyurea or growth factors are allowed).
• Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) grade >1).
• Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to selinexor dosing or strong CYP3A inducers ≤14 days prior to selinexor dosing.
• Major surgery <28 days prior to cycle 1 day 1 (C1D1).
• Uncontrolled (ie, clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participants safety, prevent the participant from giving informed consent, or being compliant with the study procedures.
• Female participants who are pregnant or lactating.
• Participants with contraindications to use of selinexor or all the drugs intended to be used in the comparative treatment arm.
Drug: Selinexor, Other: Physician's Choice Treatment
Myelofibrosis
Myelofibrosis, Selinexor, Total Symptom Score, Spleen Volume Reduction, Anemia response, TSS50, SVR35, SVR25, KPT-330, JAK1, JAK2, XPOVIO, SINE, XPORT-MF-035, Karyopharm
Phase I Study of Inotuzumab With Augmented BFM Re-Induction for Patients With Relapsed/Refractory B-cell ALL (ALL-001)
Amy Smith, BS - AJB6BB@hscmail.mcc.virginia.edu
Maher, Keri
NCT03962465
HM20020385
Inclusion Criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Diagnosed with CD-22 positive* B-cell Acute Lymphoblastic Leukemia or B-cell Lymphoblastic Lymphoma (Philadelphia chromosome negative) * For the purposes of this study, CD-22 positive will be defined based on the analysis completed for diagnostic purposes.
• Male or female, aged 16-60 years
• ECOG performance status of 0-2
• Left ventricular ejection fraction ≥ 50% measured by echocardiogram or MUGA
• Either relapsed following remission after initial induction therapy or refractory to induction therapy
• Adequate organ function, including serum creatinine ≤ 1.6 mg/dL OR creatinine clearance >50 ml/min by Cockgroft-Gault formula, bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's disease), AST, ALT and alkaline phosphatase ≤ 3 x upper limit of normal (elevation exceeding this threshold of either AST OR ALT would not meet eligibility)
• For females of reproductive potential: negative pregnancy test
• For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment
• Agreement to adhere to Lifestyle Considerations throughout study duration and for 1 year following last study treatment.
Exclusion Criteria:
• Past receipt of a total of ≥ 300 mg/m^2 doxorubicin equivalents (600 mg/m^2 daunorubicin, 60 mg/m^2 idarubicin, 75 mg/m^2 mitoxantrone)
• Current or past history of pancreatitis
• QT interval on electrocardiogram (ECG) > 0.45 by Framingham formula
• Known congestive heart failure
• Known allergy to asparaginase (only an exclusion criteria for participants enrolling in part 2)
• Presence of central nervous system (CNS) disease
• Pregnancy or lactation
• Chronic liver disease including chronic active hepatitis and/or cirrhosis
• Active Hepatitis B virus (HBV) by core antibody, surface antigen (HBsAg) or viral load
• Active Hepatitis C virus (HCV) (positive antibody test confirmed by viral load if antibody test is positive)
• Known history of infection with Human Immunodeficiency Virus (HIV)
• Active or uncontrolled infections
• Abnormal baseline hepatic ultrasound (including Dopplers)
• Prior allogeneic stem cell transplant
• Prior use of inotuzumab ozogamicin
• Known diagnosis of hemochromatosis with iron overload
• Treatment with steroids or hydroxyurea for more than 7 days with each within the 2 weeks prior to registration -that is, each is allowed for up to 7 days
• Gastrointestinal tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease, or inability to swallow medications.
• Philadelphia chromosome positive B-cell ALL
Drug: Inotuzumab ozogamicin, Drug: Prednisone Pill, Drug: Daunorubicin, Drug: Vincristine, Drug: Cytarabine, Drug: Methotrexate, Drug: Pegaspargase
B-cell Acute Lymphoblastic Leukemia
Interleukin-1 Blockade in Acute Myocardial Infarction to Prevent Heart Failure (VA-ART4)
Benjamin Van Tassell, PharmD - bvantassell@vcu.edu
Abbate, Antonio
NCT05177822
HM20022826
Inclusion Criteria:
All criteria need to be met.
* Acute ST segment elevation myocardial infarction defined as:
* chest pain, consistent with angina, within the prior 12 hours (for intermittent pain lasting more than 12 hours, the time from the when the pain became severe and constant);
* ST segment elevation on ECG \>1 mm in 2 or more anatomically contiguous leads;
* Reperfusion strategy planned or completed (including percutaneous coronary intervention or fibrinolysis)
* Age \>21 years.
Exclusion Criteria:
Subjects will not be eligible if they meet any of the following exclusion criteria.
* Pregnancy;
* Inability to obtain consent from patient;
* History of prior STEMI or of systolic heart failure (LVEF\<40%);
* Contraindications to treatment with anakinra (i.e. prior allergic reaction to Kineret® or E. coli derived products);
* Duration of chest pain \>12 hours at time of coronary artery catheterization (continuously - see exceptions in Inclusion Criteria) or coronary artery intervention \>12 hours earlier (see exceptions in Inclusion Criteria)\[max duration of chest pain 24 hours\];
* Failed reperfusion strategy (unsuccessful percutaneous coronary intervention);
* Need or plan for emergent cardiac surgery;
* Anticipated inability to complete a cardiopulmonary exercise test (CPET) on a treadmill at follow up visit at 42 days (i.e. amputee, wheel-chair bound, severe non-cardiac illness limiting mobility).
* Active infection (such as acute, i.e. COVID-19, or chronic/recurrent infectious disease i.e HBV, HCV, and HIV/AIDS-but excluding HCV+ patients with undetectable plasma RNA)
* Acute or chronic inflammatory disease or immunosuppressive therapies (including oral corticosteroids at a dose of prednisone equivalent of 0.5 mg/kg/day but not including inhaled or low dose oral corticosteroids or non-steroidal anti-inflammatory drugs).
* Neutropenia (\<1,500/mm3 or \<1,000/mm3 in African-American patients).
* Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent from complying with study instructions;
* Stage V chronic kidney disease (estimated glomerular filtration rate 15 mL/min/1.73m2 or less) or on renal-replacement therapy (a GFR ≥45 mL/min/1.73m2 is required for the cardiac magnetic resonance portion of the study);
* Limited English Proficiency that in the opinion of the investigator may prevent from understanding the content of the informed consent form and instructions during the tests required for the study.
* Any comorbidity limiting survival or ability to complete the study. DRUG: Anakinra, OTHER: Placebo
Heart Failure
Treating Heart Dysfunction Related to Cancer Therapy With Sacubitril/Valsartan (TREAT-HF)
Massey CTO CPC Team - masseycpc@vcu.edu
Bottinor, Wendy
NCT05194111
HM20023601
Inclusion Criteria:
* Age \/=40% on echocardiogram or cardiac MRI
* No symptoms of heart failure (shortness of breath, fatigue, swelling). Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
Exclusion Criteria:
* -Age \<18 years
* Inability to obtain consent from patient or legally authorized representative
* Active acute or chronic psychiatric illness that in the opinion of the investigator may prevent compliance with study instructions
* Limited English or Spanish proficiency that in the opinion of the investigator may prevent understanding the content of the informed consent form or safely completing the study procedures
* Participation in another concurrent intervention study within 30 days or treatment with an investigational drug within 5 half-lives prior to randomization
* Greater than mild mitral or aortic valve regurgitation/stenosis known pre-cancer therapy
* Severe kidney disease (GFR \<30 mL/min/1.73m2)
* Chronic hyperkalemia (\>5mmol/L)
* Evidence of COVID-19 within the last 60 days or recent (21 days) exposure to close personal contact with COVID-19.
* Greater than moderate tricuspid or pulmonary valve regurgitation/stenosis known pre-cancer therapy
* Hemodynamically significant congenital heart disease in the opinion of the investigator (not including PFO/small ASD or small VSD)
* Greater than moderate pericardial effusion
* Constrictive cardiomyopathy diagnosed pre-cancer therapy
* Family history of genetic cardiomyopathy
* Evidence of infiltrative cardiomyopathy
* Symptomatic heart disease based on NYHA classification
* Allergy to valsartan or sacubitril
* Inability to complete CMR or 6-minute walk test
* Inability to measure non-invasive blood pressure and heart rate in the ambulatory/home setting
* Pregnant/lactating
* History of severe hypersensitivity reactions to gadolinium-based contrast agents (will perform limited cardiac imaging without contrast)
* Concomitant use of other ACE inhibitors or ARBs, aliskiren, NSAIDs or lithium or the inability to stop these medications for the study DRUG: Sacubitril-valsartan, DRUG: Valsartan
Heart Failure, Heart Dysfunction
A Strategy to Prevent the Recurrence of Dental Disease in Children Receiving Dental Treatment With General Anesthesia
Jessica Gonzalez, DMD - gonzalezj13@vcu.edu
Jayaraman, Jayakumar
NCT05212142
HM20023677
Inclusion Criteria:
• parent with child (patient) planned for dental treatment with general anesthesia (GA)
• parent of a child (patient) age less than six
• parent of a child (patient) with health status of healthy (American Society of Anesthesiologists (ASA) I or II).
Exclusion Criteria:
• parents/guardians who chose not to participate in the study
• parents who spoke a language other than English or Spanish
• Parents of a child (patient) with special health care needs or patients of ASA III or IV status
Behavioral: verbal education, Behavioral: verbal education, visual aids, and motivational interviewing
Caries
DMCRN-02-001: Assessing Pediatric Endpoints in DM1 (ASPIRE-DM1)
Ruby Langeslay - ruby.langeslay@vcuhealth.org
Johnson, Nicholas, E
NCT05224778
HM20023386
Inclusion Criteria:
* Age neonate to 3 years 11 months at enrollment.
* A diagnosis of CDM, which is defined as children having symptoms of myotonic dystrophy in the newborn period (\<30 days), such as hypotonia, feeding or respiratory difficulty, requiring hospitalization to a ward or to the neonatal intensive care unit for more than 72 hours; and a genetic test confirming an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or mother. An expanded CTG repeat size in the child is considered greater than 200 repeats or E1-E4 classification (E1= 200-500, E2=500-1,000, E3=1,000-1,500, E4\>1,500).
* Guardian is willing and able to sign consent and follow study procedures
Exclusion Criteria:
* Any other non-DM1 illness that would interfere with the ability or results of the study in the opinion of the site investigator
* Significant trauma within one month
* Internal metal or devices (exclusion for DEXA component)
* History of bleeding disorder or platelet count \<50,000
* History of reaction to local anesthetic Congenital Myotonic Dystrophy, CDM
Clinical Research, Myotonic dystrophy, Congenital Myotonic Dystrophy, CDM
Prevalence of Liver Disease in Patients Dependent on Parenteral Nutrition (THRIVE-1)
Chief Scientific Operations Officer - clinicaltrials@protaratx.com
Kaspar, Matthew
NCT05011370
HM20023227
Inclusion Criteria:
• The participant and/or their parent/Legally Authorized Representative is willing and able to provide signed informed consent or assent as appropriate
• Male or female adults 18 to 80 years of age, or adolescents 12 to 17 years of age
• Patients dependent on parenteral nutrition (PN) that receive PN for an average ≥ 4 days a week for 10 weeks or longer prior to screening to meet nutritional, caloric, fluid, and/or electrolyte needs
• The Investigator expects no changes in the lipid, dextrose, amino acid, or vitamin regimen to be medically necessary during the participant's participation in the study
• Willingness of participant to maintain his/her current habitual oral diet and fluids regimen for the study duration
Exclusion Criteria:
• Participants taking steatogenic medications for ≥12 weeks in the past 12 months (e.g., amiodarone, tamoxifen, methotrexate, tetracycline, glucocorticoids, anabolic steroids, over the usual dose of estrogen for hormone replacement therapy, and valproate); those taking any medicine (e.g., metformin, thiazolidinediones, ursodeoxycholic acid, pentoxifylline, S-adenosyl-L-Methionine, and betaine) that could affect the measurement of IFALD within 12 weeks prior to study entry
• Participants taking potential hepatotoxic medications that in the judgement of the Investigator is causing hepatic abnormalities
• Participants with a cardiac pacemaker, intravascular stents, other metallic devices, and claustrophobia which are contraindicated to magnetic resonance imaging
• Participants who took choline supplements or choline-containing multivitamins within 14 days of screening
• History of major organ transplant (e.g., heart, kidney, liver, etc.) For more information on eligibility criteria, please contact the sponsor.
Intestinal Failure-associated Liver Disease
Intestinal failure-associated liver disease (IFALD), IFALD, Liver disease, Parenteral nutrition, Choline deficiency, Hepatic steatosis, Cholestasis, parenteral nutrition-associated liver disease
An Integrative Model for Palliative Care in End-Stage Liver Disease
Joel Wedd, MD, MPH - joel.wedd@vcuhealth.org
NCT05238779
Inclusion Criteria:
Primary participant:
• admission for decompensated cirrhosis, age ? 18
• willingness to sign consent
• able to read and understand English
• presence of decompensated cirrhosis with portal hypertension (jaundice, ascites, HE, hepatohydrothorax, AKI, HRS and/or variceal bleeding) or HCC Caregiver:
• identified as the primary caregiver of the participant
• age ? 18
• willingness to sign consent
• able to read and understand English
Exclusion Criteria:
Primary participant:
• prior liver transplant
• lack of capacity to provide informed consent (in the judgement of the investigator)
• already in receipt of palliative or hospice care
• those who are likely to receive a LT during the index admission Caregiver: ? none
Other: Standard of care including palliative care
End Stage Liver Disease
A Longitudinal Observational Study of Patients Undergoing Therapy for IMISC (TARGET-DERM)
Laura Dalfonso - ldalfonso@targetrwe.com
Nutan, Fnu
NCT03661866
HM20022344
Inclusion Criteria:
* 1. Adults and children (all ages) with Atopic Dermatitis or other Immune-mediated Inflammatory Skin Conditions been prescribed any dermatologic treatment.
* 2. Participant has plans for future visits at the site for continued management of IMISC.
Exclusion Criteria:
* 1. Inability to provide written informed consent/assent.
* 2. Subjects participating in any interventional study or trial for IMISC treatment trial at the time of enrollment. Patients may be enrolled in TARGET-DERM once participation in the trial is complete. Note: Participants may be enrolled in other registries or studies where IMISC treatment outcomes are observed and/or reported (such as center-based registries). Atopic Dermatitis, Alopecia Areata, Hidradenitis Suppurativa, Vitiligo, Psoriasis, Chronic Spontaneous Urticaria
Atopic Dermatitis, IMISC, Registry, Observational, Immune-mediated Inflammatory Skin Conditions