Expanding the Pool in Orthotopic Heart Transplantation

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.

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

Exclusion criteria (donors):

- Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24
antigen and/or positive HIV NAT)

- Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT) Known
ongoing therapy for HCV