Expanding the Pool in Orthotopic Heart Transplantation

NCT03222531 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY19030424
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatitis C; Heart Transplant; Cardiac Transplant

Outcome Measures

Primary Outcomes (2)

• Adverse Events

  Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

  5 years

• HCV free at 1 year

  Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

  1 year

Secondary Outcomes (5)

• Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

  5 years

• Incidence of allograft rejection

  5 years

• Incidence of graft loss

  5 years

• All-cause mortality

  5 years

• Waitlist time after enrollment

  5 years

Study Arms (2)

HCV seropositive non-viremic (HCV Ab+/NAT-) donor

EXPERIMENTAL

HCV seropositive non-viremic (HCV Ab+/NAT-) donor hearts to HCV seronegative recipients. Heart recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated. Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg). Intervention: Drug: sofosbuvir/velpatasvir

Drug: sofosbuvir/velpatasvir

HCV seropositive viremic (HCV Ab+/NAT+) donor

EXPERIMENTAL

HCV seropositive viremic (HCV Ab+/NAT+) donor hearts to HCV seronegative recipients. Starting post-operative day 1, heart recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg). Intervention: Drug: sofosbuvir/velpatasvir

Drug: sofosbuvir/velpatasvir

Interventions

sofosbuvir/velpatasvir DRUG

Drug: sofobuvir/velpatasvir

Also known as: Epclusa

HCV seropositive non-viremic (HCV Ab+/NAT-) donor; HCV seropositive viremic (HCV Ab+/NAT+) donor

Eligibility Criteria

• Age: 18 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• HCV antibody positive
• HCV NAT negative or positive
• Acceptable cardiac function for donation

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mary E. Keebler, MD: lead

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 19, 2017
• Study Start: August 1, 2017
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)