Hepatitis C, Heart Transplant, Cardiac Transplant
Conditions
Brief summary
This is an open-label, pilot trial to test the safety and efficacy of transplantation of hearts from HCV seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the heart transplant waitlist. Treatment and prophylaxis will be administered, using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).
Detailed description
This is a prospective, single center, pilot, open-label study of transplantation of hearts of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a heart from HCVAb+/NAT- donors is ARM 1 or the transmission-triggered arm of the study. In this arm, the study will monitor transmission of HCV by measuring HCV RNA in heart transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy. Recipients of a heart from HCVAb+/NAT+ donors will be in ARM 2 or the prophylaxis arm of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) on post-operative day 1 and will undergo close monitoring of HCV RNA for evidence of transmission as well as monitoring of adverse events from therapy.
Interventions
Drug: sofobuvir/velpatasvir
Sponsors
Mary E. Keebler, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
(recipients): * End stage heart failure * Age ≥ 18 and \<71 years * Listed heart transplant at UPMC * Have panel reactive antibody level of \<98% * No obvious contraindication to liver transplant * Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation * Able to provide informed consent * Be willing to use a contraceptive method for a year after transplant Inclusion criteria (donors): * HCV antibody positive * HCV NAT negative or positive * Acceptable cardiac function for donation
Exclusion criteria
(recipients): * HIV positive * HCVAb or HCV RNA positive * Presence of behavioral risk factors for contracting HCV. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting. * Hepatitis B surface antigen positive * History of liver cirrhosis * Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months * Waitlisted for a multi-organ transplant * Pregnant women * Known allergy to sofosbuvir/velpatasvir * Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study * Ongoing therapy with amiodarone for atrial or ventricular arrhythmia Prescribed use of Amiodarone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 5 years | Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group |
| HCV free at 1 year | 1 year | Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation |
Secondary
| Measure | Time frame |
|---|---|
| Waitlist time after enrollment | 5 years |
| Incidence of graft loss | 5 years |
| Incidence of allograft rejection | 5 years |
| Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients | 5 years |
| All-cause mortality | 5 years |
Countries
United States
Outcome results
None listed