Expanding the Pool in Orthotopic Heart Transplantation

Phase 2

Active, not recruiting

• Conditions: Heart Transplant; Hepatitis C; Cardiac Transplant
• Interventions: Drug: sofosbuvir/velpatasvir

• Registration Number: NCT03222531
• Lead Sponsor: Mary E. Keebler, MD

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.

Study Timeline

• Study First Submitted: 2017-07-05
• Study First Submitted QC: 2017-07-17
• Study First Posted: 2017-07-19
• Study Start: 2017-08-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-02-03
• Last Update Posted: 2025-02-04
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HCV seropositive viremic (HCV Ab+/NAT+) donor	sofosbuvir/velpatasvir	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
HCV seropositive non-viremic (HCV Ab+/NAT-) donor	sofosbuvir/velpatasvir	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Incidence of allograft rejection	5 years
Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients	5 years
All-cause mortality	5 years
Waitlist time after enrollment	5 years
Incidence of graft loss	5 years

Trial Locations

Locations (1)

UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States