End Stage Renal Disease
Conditions
Brief summary
The Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients \[THINKER-NEXT\] study will include adult kidney transplant candidates without hepatitis C virus (HCV) infection on the transplant waiting list who will consent to kidney transplantation from a deceased donor infected with HCV, followed by treatment with a direct acting antiviral. The one-year allograft function and one-year risk of CMV infection will be compared between THINKER-NEXT kidney transplant recipients and matched recipients who received hepatitis C uninfected kidney transplants (these patients are called Transplant Cohort). The survival rate of patients opting-in for offers of kidneys from HCV-viremic donors will be compared to the survival rate of matched comparators from the kidney transplant waitlist who did not consent to receive offers of a HCV-viremic kidney. Lastly, renal pathologic findings will be compared among HCV-viremic donors and HCV-negative comparator donors.
Interventions
DRUGEpclusa
All patients will receive 12 weeks of sofosbuvir/velpatasvir as per the FDA label.
Sponsors
University of Pennsylvania
Gilead Sciences
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to provide informed consent * Active waiting list status for isolated kidney transplant * 18 years of age or older * No living kidney donor * Panel reactive antibody (PRA) ≤97% (most recent cPRA at time of screening). Patients with a PRA of 98-100% at screening can be included unless patient has a most recent cytotoxic PRA of \>25% or calculated PRA \>50% where multiple moderate level HLA antibodies exist and in the opinion of the local site investigator represents substantial HLA sensitization. If patient has a PRA of 98-100%, the donor-recipient pair must meet additional eligibility criteria.
Exclusion criteria
* Hepatocellular carcinoma * Hepatitis B surface antigen and/or DNA positive * Active Hepatitis C infection * HIV RNA-positive or HIV antibody positive * Other chronic liver disease (excluding non-alcoholic fatty liver disease \[NAFLD\] with normal liver enzymes) * Persistently elevated liver transaminases (defined as the upper limit of normal at the reference laboratory) * Advanced hepatic fibrosis or cirrhosis * Primary Focal Segmental Glomerulosclerosis (FSGS), FSGS recurring in initial transplant, or other disease process at high risk of early graft failure per the treating transplant nephrologist * Current use of amiodarone or dronedarone (due to interaction with sofosbuvir) * Transplant candidate requires antibody desensitization protocol for transplantation * Female who is pregnant, planning to become pregnant during the study, or breast-feeding * Participation in another interventional study, from a period starting 6 months prior to screening to last study visit, that the study PIs judge would interfere with either the aims or the safety of the THINKER-NEXT study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-treatment sustained virologic response (SVR) to direct-acting antiviral (DAA) | Baseline to 24 weeks | The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR-12; negative HCV RNA 12 weeks after completing Epclusa therapy)/(number of subjects treated with Epclusa post-kidney transplantation) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPeter Reese, MD, PhD
University of Pennsylvania
Outcome results
None listed