Expanding the Pool in Orthotopic Heart Transplantation

Hepatitis C Clinical Trial

Official title:

Expanding the Pool in Orthotopic Heart Transplantation: The Use of Hepatitis C Positive Donor Hearts in Hepatitis C Negative Recipients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03222531
• Other study ID #: STUDY19030424
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 71 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Transplant
• Heart Transplant
• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• sofosbuvir/velpatasvir
Drug: sofobuvir/velpatasvir

Locations

Country	Name	City	State
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Mary E. Keebler, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group	5 years
Primary	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	Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients		5 years
Secondary	Incidence of allograft rejection		5 years
Secondary	Incidence of graft loss		5 years
Secondary	All-cause mortality		5 years
Secondary	Waitlist time after enrollment		5 years