Liver Transplant, Hepatitis C
Conditions
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.
Interventions
12 week, oral, fixed dose
Sponsors
University of Pittsburgh Medical Center
Fernanda P Silveira, MD, MS
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 5 years | Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of graft loss | 5 years | Incidence of graft loss at 5 years |
| Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients | 5 years | Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients |
| Waitlist time after enrollment | 5 years | Waitlist time after enrollment |
| All-cause mortality | 5 years | All-cause mortality at 5 years |
| Incidence of allograft rejection | 5 years | Incidence of allograft rejection at 5 years |
Countries
United States
Outcome results
None listed