Heart Failure Clinical Trial
— USHEROfficial title:
Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors
Verified date | November 2021 |
Source | University of Pennsylvania |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study is being conducted to determine safety and effectiveness of transplanting hearts from Hepatitis C-positive donors into Hepatitis C-negative patients on the heart transplant waitlist, who will then be treated with Zepatier after transplantation.
Status | Completed |
Enrollment | 20 |
Est. completion date | November 30, 2019 |
Est. primary completion date | September 10, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - New York Heart Association (NYHA) Class III or IV CHF refractory to maximal medical therapy (ACE inhibitor, B-blocker, digoxin and diuretics, resynchronization therapy or Implantable Cardioverter Defibrillator when applicable) and/or conventional surgery. - Inoperable coronary artery disease with intractable anginal symptoms - Malignant ventricular arrhythmias unresponsive to medical or surgical therapy - 18-65 years of age - Obtained agreement for participation from the transplant cardiology team - No evident contraindication to liver transplantation other than the underlying cardiac disorder - Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation - No active illicit substance abuse - Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage - Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HCV transmission - Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-heart transplantation - Able to provide informed consent Exclusion Criteria: - Hepatocellular carcinoma - HIV positive - HCV antibody positive and/or RNA positive - Hepatitis B surface antigen, core antibody, and/or DNA positive - Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes - Persistently elevated liver transaminases - Congenital heart disease - Fibrosis by liver biopsy or total bilirubin > 2.5 with associated evidence of synthetic dysfunction. - Pregnant or nursing (lactating) women - Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and ZEPATIER - Waitlisted for a multi-organ transplant - Evidence of end organ damage due to diabetes (e.g. retinopathy, nephropathy, ulcerations) and /or brittle diabetes mellitus (e.g. history of diabetic ketoacidosis) and/or uncontrolled diabetes as evidence by a HgbA1C of 7.5-8.5. - Chronic bronchitis, chronic obstructive pulmonary disease, inability to stop smoking. - Hematologic: Significant coagulation abnormalities, bleeding diatheses. - Psychosocial: Profound neurocognitive impairment with absence of social support. - Active mental illness or psychosocial instability - Inadequate insurance or financial support for post-transplant care. - Evidence of drug, tobacco or alcohol abuse within the past six months and completion of recommended therapy/services or meets satisfied parameters as indicated by social work staff and/or consult team. - History of chronic non-compliance. - Amyloidosis (restricted to cardiac only, without evidence of extra cardiac involvement) - BMI =38 - Active peptic ulcer disease. - Severe malnutrition. - Major chronic disabling illness (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual). - Pulmonary infarction within the past 6 weeks - Severe pulmonary hypertension as evidenced by a fixed pulmonary vascular resistance of greater than 4 Wood units on appropriate medical therapy. - Patient refusal to receive blood products or transfusions during heart transplant surgery. - Severe chronic obstructive pulmonary disease - Current clinical sepsis. - Symptomatic or severe vascular disease. - Chronic Kidney Disease Stage IV, Glomerular Filtration Rate < 30 - History of Mantle radiation. - Asymptomatic renal cell carcinoma <1 year from curative treatment. - Symptomatic renal cell carcinoma <5 years from curative treatment. - Prostate cancer <2 years from curative treatment. - Uterine or cervical cancer <2 years from curative treatment. - Any other cancer other than the above including malignant melanoma, < 5 years from treatment apart from other skin malignancies. Donor Organ Selection Criteria: General criteria (although there can be exceptions on a case-by-case basis) - Detectable HCV RNA - Genotype 1 or 4 HCV - Age <=55 years - No history of coronary artery disease - No congenital heart disease except a repaired atrial septal defect (ASD) provided the patient has normal right ventricular function - No history of arrhythmia (atrial fibrilation, atrial flutter or VT) except during resuscitation from fatal event. - No evidence of cirrhosis Echocardiographic criteria: - Left ventricular ejection fraction (LVEF) >=50% - Normal right ventricular function - No left ventricular hypertrophy (LVH) - septal wall thickness <1 cm - No left ventricular hypertrophy (LVH)- posterior wall thickness <1 cm - No significant valvular heart disease - more than mild tricuspid regurgitation, more than mild mitral regurgitation, more than trace aortic regurgitation. No mitral or aortic stenosis. - No congenital heart disease - transposition of the great vessels, ventricular septal defect (VSD), ASD, and/or single ventricle (Fontan) Right heart catheterization criteria: - Right atrial pressure <=10mmHg - Pulmonary capillary wedge pressure <=18mmHg - CI >=2.1 l/min/m2 - Pulmonary hypertension is allowed if the patient has normal right ventricular function and a normal tricuspid valve |
Country | Name | City | State |
---|---|---|---|
United States | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
University of Pennsylvania | Merck Sharp & Dohme Corp. |
United States,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants With Post-treatment Sustained Virologic Response (SVR) | The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation) | Baseline to 24 weeks | |
Primary | Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant | Baseline to 52 weeks |
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