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

November 18, 2021 updated by: University of Pennsylvania

Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Open-labelled pilot clinical trial of Zepatier (MK-5172 and MK-8742/Grazoprevir + Elbasvir) in at least 20 HCV-negative subjects receiving a heart transplant from a HCV-positive donor. Eligible subjects will receive a heart transplant from a deceased-donor with genotype 1 or 4 HCV, and then will receive 12 weeks of Zepatier after heart transplantation when infection with HCV is confirmed in these heart transplant recipients. Treatment will be complete after 12 weeks.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zepatier (grazoprevir 100mg and elbasvir 50 mg)
Drug: Zepatier
Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Post-treatment Sustained Virologic Response (SVR)
Time Frame: Baseline to 24 weeks
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
Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant
Time Frame: Baseline to 52 weeks
Baseline to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Peter Reese, MD, MSCE, Perelman School of Medicine at the University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2017

Primary Completion (Actual)

September 10, 2019

Study Completion (Actual)

November 30, 2019

Study Registration Dates

First Submitted

April 27, 2017

First Submitted That Met QC Criteria

May 8, 2017

First Posted (Actual)

May 10, 2017

Study Record Updates

Last Update Posted (Actual)

November 22, 2021

Last Update Submitted That Met QC Criteria

November 18, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 826708

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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