A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients

Phase 2

Active, not recruiting

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Epclusa (sofosbuvir/velpatasvir)	Epclusa	Epclusa is taken by mouth for 12 weeks as per the FDA label.

Primary Outcome Measures

Name	Time	Method
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)

Secondary Outcome Measures

Name	Time	Method

Locations (11): University of Alabama at Birmingham
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Birmingham, Alabama, United States
University of Florida
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Gainesville, Florida, United States
Jackson Memorial Hospital/University of Miami
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Miami, Florida, United States
Johns Hopkins
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Baltimore, Maryland, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
New York Presbyterian Hospital/Columbia University
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New York, New York, United States
University of Cincinnati
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Cincinnati, Ohio, United States
Cleveland Clinic
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Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Medical University of South Carolina
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Charleston, South Carolina, United States
Vanderbilt University
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Nashville, Tennessee, United States