StudyFinder
Search Results Within Category "Muscle & Bone Health"
7 Study Matches
Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention (PROSe-ICD)
Katherine Wu, MD - kwu@jhmi.edu
NCT00733590
Inclusion Criteria:
* History of acute MI at least 4 weeks old
* Non-ischemic LV dysfunction for at least 9 months
* Who have an ejection fraction (EF) \< or = to 35%
* Undergone elective replacement indicator (ERI) generator replacement of an FDA-approved ICD for primary prevention of SCD within 24 months of enrollment.
* Who have primary prevention implants.
Exclusion Criteria:
* ICD generator replacement for secondary prevention
* Inability or unwillingness to provide valid informed consent
* New York Heart Association Class IV heart failure
* Patients with pre-existing Class 1 indications for pacemaker therapy. Heart Failure, Congestive, Death, Sudden, Cardiac, Arrhythmia, Cardiomyopathies
defibrillator, implanted, genomics, electrocardiography, electrophysiological study, proteomics
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
Gwaltney, Lindsey - lbgwaltney@vcu.edu
Boomer, Laura, A
NCT05235165
HM20024392
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* 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: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma
A Study to Evaluate the Safety and Efficacy of CNTX-6970 in Subjects With Knee Osteoarthritis Pain.
Aderonke Pederson, MD - apederson@mgh.harvard.edu
NCT05025787
A subject will be eligible for study participation if they meet all of the following
criteria:
• Individuals between 40 and 90 years of age (inclusive) at the time of the Screening Visit.
• Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use.
• Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications.
• Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 1, 2, 3, or 4. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.
• Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator.
• Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.
• Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator.
• Body mass index (BMI) of ≤ 40 kg/m2.
• Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points. A subject will be excluded from the study if they meet any of the following criteria:
• Any form of joint replacement surgery, open surgery, or arthroscopic surgery of the index knee/knee joint with 12 months of Screening.
• Any painful condition(s) of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee.
• Other chronic pain anywhere in the lower extremities (e.g. hips, legs, feet) that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications. This includes radicular low back pain with radiation to the knee.
• Documented history of neuropathic arthropathy in the knee.
• Significant instability (e.g., cruciate ligament tear or rupture or previous repair) within the past 5 years or current misalignment (>10 degrees varus or valgus) of the index knee.
• Plans to have surgery, invasive procedures, or intra-articular (IA) injections of the index knee or procedure or surgery otherwise contraindicated for study participation while in the study. a. Concomitant Medications for Pain - i. Continuous use of one of the following medications prescribed for pain: tramadol, gabapentin, duloxetine, pregabalin, milnacipran, or tricyclic antidepressants that is:
• chronic for at least 12 weeks; and
• at a stable dose for at least 4 weeks before Screening ii. Intermittent use of opioids that is:
• ongoing for at least 4 weeks before Screening;
• at a frequency no more than 4 days/week; and
• not be taken within 24 hours of a study visit iii. As needed use of acetaminophen b. Concomitant Medications for Non-Pain Indications That May Impact Pain - i. Continuous use of medication for non-pain indications that are known to potentially impact pain, e.g. duloxetine for depression, that is at a stable dose for at least 12 weeks prior to Screening.
• Corticosteroid injection in the index knee within 90 days of Screening or during study participation.
• Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening or any time during study participation.
• History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa drugs.
• Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.
• Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).
• Individuals between 40 and 90 years of age (inclusive) at the time of the Screening Visit.
• Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use.
• Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications.
• Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 1, 2, 3, or 4. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.
• Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator.
• Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.
• Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator.
• Body mass index (BMI) of ≤ 40 kg/m2.
• Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points. A subject will be excluded from the study if they meet any of the following criteria:
• Any form of joint replacement surgery, open surgery, or arthroscopic surgery of the index knee/knee joint with 12 months of Screening.
• Any painful condition(s) of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee.
• Other chronic pain anywhere in the lower extremities (e.g. hips, legs, feet) that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications. This includes radicular low back pain with radiation to the knee.
• Documented history of neuropathic arthropathy in the knee.
• Significant instability (e.g., cruciate ligament tear or rupture or previous repair) within the past 5 years or current misalignment (>10 degrees varus or valgus) of the index knee.
• Plans to have surgery, invasive procedures, or intra-articular (IA) injections of the index knee or procedure or surgery otherwise contraindicated for study participation while in the study. a. Concomitant Medications for Pain - i. Continuous use of one of the following medications prescribed for pain: tramadol, gabapentin, duloxetine, pregabalin, milnacipran, or tricyclic antidepressants that is:
• chronic for at least 12 weeks; and
• at a stable dose for at least 4 weeks before Screening ii. Intermittent use of opioids that is:
• ongoing for at least 4 weeks before Screening;
• at a frequency no more than 4 days/week; and
• not be taken within 24 hours of a study visit iii. As needed use of acetaminophen b. Concomitant Medications for Non-Pain Indications That May Impact Pain - i. Continuous use of medication for non-pain indications that are known to potentially impact pain, e.g. duloxetine for depression, that is at a stable dose for at least 12 weeks prior to Screening.
• Corticosteroid injection in the index knee within 90 days of Screening or during study participation.
• Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening or any time during study participation.
• History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa drugs.
• Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.
• Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).
Drug: Celecoxib, Drug: CNTX-6970, Drug: Placebo
Knee Osteoarthritis
A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma
ctrrecruit@vcu.edu
NCT05691478
Inclusion Criteria:
* Patients must be \< 40 years of age at the time of enrollment.
* Patients must have a body surface area of \>= 0.8 m\^2 at the time of enrollment.
* Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
* Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
For this study, metastatic disease is defined as one or more of the following:
* Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
* Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions \>= 5 mm, OR multiple pulmonary lesions \>= 3 mm or greater in size.
* Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
* Efficacy Phases (Phase 2/3) NOTE: as of Amendment #2B, the efficacy phase is open for enrollment.
Patients with both localized and metastatic disease are eligible for the efficacy phase, regardless of resectability. Patients will be enrolled to two separate cohorts:
* Cohort 1 (Standard Risk): Patients with non-pelvic primary osteosarcoma deemed to be resectable at the time of diagnosis by the institutional multidisciplinary team, without evidence of metastatic lesions.
* Cohort 2 (High-Risk): Patients with a primary pelvic tumor, a primary tumor designated as unresectable by the institutional multidisciplinary team, AND/OR radiographic evidence of metastatic lesions.
* A serum creatinine based on age/sex as follows (within 7 days prior to enrollment unless otherwise indicated):
* (Age: Maximum Serum Creatinine \[mg/dL\]; Sex)
* 1 month to \< 6 months: 0.4 (male); 0.4 (female)
* 6 months to \< 1 year: 0.5 (male); 0.5 (female)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* OR - a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2
* OR - a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment unless otherwise indicated)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment unless otherwise indicated)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias
* Shortening fraction of \>= 27%, or
* Ejection fraction of \>= 50%
* Corrected QT interval by Fridericia (QTcF) \< 480 msec on electrocardiogram. Patients with Grade 1 prolonged QTc (450-480 msec) at time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications).
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment unless otherwise indicated)
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) (within 7 days prior to enrollment unless otherwise indicated)
* Hemoglobin \>= 8.0 g/dL (within 7 days prior to enrollment unless otherwise indicated)
* International normalized ratio (INR) =\< 1.5 (within 7 days prior to enrollment unless otherwise indicated)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4, CYP2D6, and/or MRP2 transporter protein.
* 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.
Exclusion Criteria:
* Patients who have received previous systemic therapy for osteosarcoma or a prior oncologic diagnosis.
* Patients who have central nervous system metastases.
* Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung.
* Patients who are unable to swallow tablets. Tablets cannot be crushed or chewed.
* Patients with gastrointestinal disorders including active disorders associated with a high risk of perforation or fistula formation. Specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, bowel obstruction, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
* Patients with active bleeding or bleeding diathesis. No clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding within 3 months prior to enrollment.
* Patients with uncompensated or symptomatic hypothyroidism. Patients who have hypothyroidism controlled with thyroid replacement hormone are eligible.
* Patients with moderate to severe hepatic impairment (Child-Pugh B or C).
* Patients who have had primary tumor resection or attempted curative resection of metastases prior to enrollment.
* Patients who have undergone other major surgical procedure (eg, laparotomy) within 14 days prior to enrollment. Thoracoscopic procedures for diagnostic purposes (biopsy of lung nodule) and central access such as port-a-cath placement are allowed.
* Patients with a history of serious or non-healing wound or bone fracture (pathologic fracture of primary tumor is not considered exclusion).
* Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of cabozantinib.
* Patients with previously identify allergy or hypersensitivity to components of the study treatment formulations.
* Patients who are receiving any other investigational agent not defined within this protocol are not eligible.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
* Patients who received enzyme-inducing anticonvulsants within 14 days prior to enrollment.
* Patients with a prior history of hypertension (\> 95th percentile for age, height, and sex for patients \< 18 years and \> 140/90 mmHg for patients \>= 18 years requiring medication for blood pressure control.
* Patients who are receiving drugs that prolong QTc.
* Patients receiving anticoagulation with oral coumarin agents (eg warfarin), direct thrombin inhibitors (eg dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (eg, clopidogrel). Low dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH and direct factor Xa inhibitors rivaroxaban or apixaban are allowed in subjects who are on a stable dose for at least 6 weeks before the first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
* Patients receiving strong CYP3A4 inducers or strong CYP3A4 inhibitors.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of protocol therapy. PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, PROCEDURE: Surgical Procedure, PROCEDURE: X-Ray Imaging
High Grade Osteosarcoma, Localized Osteosarcoma, Metastatic Osteosarcoma, Secondary Osteosarcoma
Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma (STRASS2)
EORTC HQ - 1809@eortc.org
NCT04031677
• STRASS 2
Inclusion Criteria:
* Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
* LMS:
* Any grade LMS can be included
* Minimum size of LMS tumor should be 5 cm
* LPS:
* Diagnosis should be confirmed based on MDM2 (Mouse double minute 2 homolog) and CDK4 (Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while proof of MDM2 amplification is highly recommended.
* All grade 3 DDLPS can be included.
* DDLPS with confirmed grade 2 on biopsy can be included when:
* The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy).
* The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
* Unifocal tumour
* Resectable tumour: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcoma team. A patient is not considered resectable when the expectation is that only an R2 resection is feasible.
* Criteria for non-resectability are:
* Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein
* Involvement of bone
* Growth into the spinal canal
* Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium
* Infiltration of multiple major organs like liver, pancreas and or major vessels
* Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. CT thorax abdomen pelvis with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen \& pelvis
* Collection of tumour tissue for central pathology review is mandatory.
* For patients with LMS: if there is not enough tissue for assessing the grading, this is acceptable.
* If tumour tissue is not available for the central pathology review, patient will not be eligible.
* If the biopsy was not done or the FFPE of the biopsy not available but at least 10 unstained slides or one pathological block are available for the central review, that will be considered as acceptable.
* For the biopsy if fine needle aspiration (FNA) is performed instead of core needle biopsy (CNB) recommended by the standard guidelines, please contact the EORTC medical monitors for further evaluation.
* Collection of tumour tissue and blood samples for translational research is mandatory.
* In case there is not enough tissue for TR, a new biopsy is not required and if the patient fulfils all other eligibility criteria, he/she will be eligible.
* If the blood samples are not collected, patient will not be eligible.
* If the patient refuses the collection of biomaterial for TR, patient will not be eligible even if he/she fulfils all other eligibility criteria
* ≥ 18 years old (no upper age limit)
* WHO performance status ≤ 2
* Adequate haematological and organ function
* American Society of Anaesthesiologist (ASA) score \< 3
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
Note: a woman is considered of childbearing potential, i.e., fertile, if she is following menarche. She remains of childbearing potential until she becomes post-menopausal or permanently sterile.Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 consecutive months without menses, a single FSH measurement is insufficient.
* WOCBP in both arms should use highly effective birth control measures, during the study treatment period and for at least 6 months after the last dose of chemotherapy or date of surgery (except for women receiving chemotherapy with ifosfamide who should continue contraception until 1 year after last day of treatment). A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
* For men in the experimental arm: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
* Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6months after the last study treatment.
* Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria:
* Sarcoma originating from bone structure, abdominal or gynecological viscera
* Extension through the sciatic notch or across the diaphragm
* Metastatic disease
* Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour
* Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
* Congestive heart failure
* Angina pectoris
* Myocardial infarction within 1 year before randomization
* Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy.
Note: in case of high blood pressure: 1) initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 2) blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 150/90mmHg in order for a patient to be eligible for the study.
* Uncontrolled cardiac arrhythmia
* Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Active and uncontrolled infections
* Vaccination with live vaccines within 30 days prior to study entry
* Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
* Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer.
* Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum.
* Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
* Known contraindication to imaging tracer and to MRI
• Selection criteria for STREXIT 2 * Patients with histologically proven primary resectable localized high-risk DDLPS or LMS of retroperitoneal space or infra-peritoneal spaces of pelvis (as described in the inclusion criteria of STRASS 2) and amenable to receive chemotherapy but for whom the list of eligibility criteria for the study is too restrictive (tumour grading not available, inadequate organ function, concomitant diseases) * Patients who meet all eligibility criteria of STRASS 2 but do not consent to randomization or are not enrolled for any other reason. * Patients enrolled in a Registry collecting data on primary RPS patients in the centres participating in STRASS 2 (e.g., RESAR) and who satisfy the above criteria.
• Selection criteria for preferences for neoadjuvant chemotherapy in STRASS 2 substudy All patients recruited to STRASS 2 in participating centres (Australia +/- international sites) that are able to read, comprehend and write in English at a sufficient level to complete study materials.
PROCEDURE: Surgery, DRUG: Preoperative chemotherapy
Retroperitoneal Sarcoma, Liposarcoma, Leiomyosarcoma
Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator (CARVTOP-ICD)
Mehmet Aktas, M.D. - Mehmet_Aktas@URMC.Rochester.edu
NCT06964464
Inclusion Criteria:
* Age ≥ 18 years
* ICD implanted for primary prevention for HFrEF (either ICM or NICM) with remote monitoring capability
* Current treatment with metoprolol succinate and willing to switch to carvedilol
* LVEF \<50% during the past 12 months prior to consent
Exclusion Criteria:
* Unwilling or unable to follow the protocol
* Treatment with any other ßB than metoprolol succinate or no ßB treatment
* Known prior intolerance or contraindication to carvedilol
* Systolic blood pressure \<100 mmHg
* Enrollment in another clinical trial
* Inability or unwilling to consent DRUG: Metoprolol Succinate, DRUG: Carvedilol
Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
Medical Information - medinfo@eidostx.com
NCT06563895
Key
Inclusion Criteria:
* Male or female ≥ 18 to ≤ 75 years of age inclusive.
* Participants must have an established genotype (hetero- or homozygosity) of a TTR gene variant that is known to be pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or any other pathogenic TTR variant(s)) confirmed by central laboratory prior to randomization.
* Participant's age is no more than 10 years (≤ 10) younger than the PADO.
Key Exclusion Criteria:
* Evidence of ATTR-CM or ATTR-PN.
* Presence of a TTR variant known to be phenotypically protective (eg, T119M, R104H).
* Current or past treatment with other TTR modifying therapies.
* Contraindication to or inability to undergo Cardiac magnetic resonance testing.
* Major organ dysfunction, including: kidney disease, liver disease, heart disease (including cardiomyopathy), neuropathy
* Other diseases or conditions such has cancer within 3 years, untreated hyperthyroidism or hypothyroidism, type 1 diabetes, active hepatitis B or C, HIV.
* Major surgery within the past 3 months or planned during the next 12 months.
* Known hypersensitivity to acoramidis. DRUG: Acoramidis, DRUG: Placebo oral tablet
Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies
Amyloidosis, ATTR-CM, ATTR-PN, Transthyretin, Amyloid, TTR