Preemptive Zepatier Treatment in Donor HCV Positive to Recipient HCV Negative Cardiac Transplant

Study Overview
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Brief Summary
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This is a proof of concept, single center study for the donation of HCV-positive hearts to HCV negative recipient patients, with preemptive, interventional treatment with 12-16 weeks of grazoprevir and elbasvir (with or without ribavirin) to prevent HCV transmission upon transplantation.

Detailed Description
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Phase 1 of this study will be a single case study with only one subject enrolled. Once safety has been demonstrated and HCV infection transmission shown to be prevented by the protocol, the study will expand to 10 additional patients. Patients will be selected based on their diminished likelihood of receiving a heart from the waitlist within a period during which they would be likely to succumb to severe comorbidities. This will be determined in part through use of a patient's listing status (1A, 1B, 2) and clinical judgment, and the Seattle Heart Failure Model.

Official Title
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A Proof of Concept Study for Preemptive Treatment With Grazoprevir and Elbasvir in Donor HCV-positive to Recipient HCV-negative Cardiac Transplant

Conditions
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Cardiac Transplant Disorder, Hepatitis C

Intervention / Treatment
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* Drug: Combindation treatment with Grazoprevir and Elbasvir fixed dose combination tablet, with or without ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient is Age ≥ 18 years Serum ALT within normal limits with no history of liver disease Lack of sensitization (i.e. PRA < 20%) that would be expected to result in a high likelihood of needing aggressive immunosuppression to treat rejection Exclusion Criteria: Sensitization (i.e. PRA >20%) Any liver disease in recipient Albumin < 3g/dl or platelet count < 75 x 103/mL Need for dual organ transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with grazoprevir + elbasvir +/- ribavirin<br>12 to 16 weeks of treatment with combination tablet of grazoprevir + elbasvir +/- ribavirin | Drug: Combindation treatment with Grazoprevir and Elbasvir fixed dose combination tablet, with or without ribavirin<br>* HCV treatment for 12 to 16 weeks. Treatment length and addition of ribavirin based upon presence of baseline resistance associated variant in the HCV virus. Medications given concurrently.<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable HCV | Negative HCV viral RNA at 12 weeks after the last dose of treatment. | 12 Weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability (based on number of adverse events and out of range lab values) of grazoprevir and elbasvir (with or without ribavirin) in patients who have undergone cardiac transplantation | Safety and tolerability of grazoprevir and elbasvir in the cardiac transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient. | Upto 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Transplant, Cardiac Transplant, Hepatitis C, Zepatier