Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors (HCV)

• Status: Completed
• Trial end date: 2019-11-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Elbasvir-grazoprevir drug combination

Criteria

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