The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients

Phase 2CompletedNCT03819322

Fernanda P Silveira, MD, MS73 enrolled

Overview

This is an open-label, pilot trial to test the safety and efficacy of transplantation of livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver 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).

This is a prospective, single center, pilot, open-label study of transplantation of livers of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor transmission of HCV by measuring HCV RNA in liver 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 liver from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for evidence of transmission. To be eligible for the study, subjects need to be listed for liver transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Transplant Hepatitis C

Interventions

sofosbuvir/velpatasvirDRUG

12 week, oral, fixed dose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria (recipients): 1. Patients with end-stage liver disease listed for liver transplantation at UPMC. 2. Age ≥ 18 3. No available living liver donor 4. Listed for an isolated liver transplant at UPMC 5. Have panel reactive antibody level of \<98% 6. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation 7. Able to provide informed consent 8. Be willing to use a contraceptive method for a year after transplant Exclusion criteria (recipients): 1. HIV positive 2. HCVAb or HCV RNA positive 3. 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. 4. Hepatitis B surface antigen positive 5. History of atrial fibrillation requiring the use of amiodarone over the past 12m 6. Receipt of prior organ transplant 7. Waitlisted for a multi-organ transplant 8. Pregnant women 9. Known allergy to sofosbuvir/velpatasvir 10. 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 Inclusion criteria (donors): 1. HCV antibody positive 2. HCV NAT negative or positive Exclusion criteria (donors): 1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT) 2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT) 3. Known ongoing therapy for HCV

Locations (1)

UPMC

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

Adverse events

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

Time frame: 5 years

HCV free at 1 year

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

Time frame: 1 year

Secondary Outcomes

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

Time frame: 5 years

Incidence of allograft rejection

Incidence of allograft rejection at 5 years

Time frame: 5 years

Incidence of graft loss

Incidence of graft loss at 5 years

Time frame: 5 years

All-cause mortality

All-cause mortality at 5 years

Time frame: 5 years

Waitlist time after enrollment

Time frame: 5 years

Data from ClinicalTrials.gov

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