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
Fernanda P Silveira, MD, MS
University of Pittsburgh Medical Center
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 Due to Sofosbuvir/Velpatasvir (Epclusa) | 5 years | Adverse events due to sofosbuvir/velpatasvir (Epclusa) |
| HCV Free at 1 Year Following Transplantation | 1 year | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transmission Rate of HCV From HCVAb+/NAT- Donors to HCVAb- Recipients | 5 years | — |
| Incidence of Allograft Rejection at 5 Years | 5 years | — |
| Incidence of Graft Loss at 5 Years | 5 years | — |
| All-cause Mortality at 5 Years | 5 years | — |
| Waitlist Time After Enrollment | 5 years | In days |
Countries
United States
Contacts
STUDY_DIRECTORFernanda Silviera, MD
University of Pittsburgh
PRINCIPAL_INVESTIGATORNaudia Jonassaint, MD
University of Pittsburgh
Participant flow
Pre-assignment details
73 participants signed informed consent. 68 participants were not eligible and not considered enrolled due to: transplanted with a liver from an HCV seronegative donor (37 participants); death on the waitlist (11 participants); transplant candidacy declined (7 participants); removal from the waitlist (6 participants); prior history of HCV (1 participant); still waitlisted (6 participants). 5 participants met eligibility criteria and were considered enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69 Years STANDARD_DEVIATION 0 |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 4 |
| other Total, other adverse events | 0 / 1 | 0 / 4 |
| serious Total, serious adverse events | 0 / 1 | 0 / 4 |
Outcome results
None listed