Clinical trial NCT03819322: The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients
Official title: Transplantation of Livers of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa®)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Liver Transplant
Hepatitis C
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh Medical Center
First posted: 2019-01-28
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: 5 years
measure: HCV free at 1 year
timeFrame: 1 year
Secondary outcomes:
measure: Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
timeFrame: 5 years
measure: Incidence of allograft rejection
timeFrame: 5 years
measure: Incidence of graft loss
timeFrame: 5 years
measure: All-cause mortality
timeFrame: 5 years
measure: Waitlist time after enrollment
timeFrame: 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Fernanda Silviera, MD
role: STUDY_DIRECTOR
affiliation: University of Pittsburgh
name: Naudia Jonassaint, MD
role: PRINCIPAL_INVESTIGATOR
References: