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 HCV cure rate will be determined for all recipients of HCV-viremic kidneys. The mortality rate of kidney transplant candidates who enroll in THINKER-NEXT and consent to offers of kidneys from HCV-viremic donors will be compared to matched wait-listed patients who do not consent to receive HCV-viremic kidneys (these patients are the Matched Wait-list Cohort). The one-year allograft function will be compared between THINKER-NEXT kidney transplant recipients and matched recipients at similar centers who received hepatitis C uninfected kidney transplants (this analysis will involve a matched Transplant Cohort 1). The one-year risk of cytomegalovirus (CMV) infection will be compared between THINKER-NEXT kidney transplant recipients and matched recipients who received hepatitis C uninfected kidney transplants at THINKER-NEXT centers (this analysis will involve matched Transplant Cohort 2). Renal pathologic findings will be compared between HCV-viremic donor kidneys and HCV-negative comparator donor kidneys.

The study population includes kidney transplant candidates and recipients. Active follow-up will be for one year with additional passive follow-up for up to five years. Participants will be enrolled at eight clinical centers in the United States. The overarching goal of this trial is to determine if kidneys from HCV-viremic donors can safely be transplanted into HCV-negative patients with end-stage renal disease. If the results of this trial demonstrate that this practice is safe and effective, these efforts could extend and improve life for hundreds of patients each year by opening up a new path to DDKT.

To estimate the hepatitis C virus (HCV) cure rate after transplantation using kidneys from HCV-viremic deceased donors for HCV-negative recipients, followed by treatment with direct acting antivirals.

• To determine whether consenting to being transplanted with a kidney from an HCV-viremic donor is associated with a superior survival versus waiting for an HCV-negative kidney
• To determine if one-year allograft function is non-inferior for HCV-negative patients transplanted with a kidney from an HCV-viremic donor versus an HCV-negative kidney
• To determine whether the incidence of CMV infection is increased among HCV-negative patients transplanted with an HCV-viremic kidney versus an HCV-negative kidney
• To determine if the prevalence of chronic disease pathology is similar in peri-transplantation (pre-procurement or time-zero) biopsies of kidneys from HCV-viremic donors versus comparator kidneys from HCV-negative deceased donors

The primary endpoint is hepatitis c virus (HCV) cure rate as measured by SVR-12 (sustained virologic response after 12 weeks post-treatment). The secondary endpoints will be measured by death; one-year allograft function; CMV infection; and chronic disease pathology in the donated kidney, such as interstitial fibrosis and glomerulosclerosis.

• Able to provide informed consent
• Active waiting list status for isolated kidney transplant
• 18 to 70 years of age
• No living kidney donor
• Panel reactive antibody (PRA) ≤97% (most recent cPRA at time of screening)

• Hepatocellular carcinoma
• Hepatitis B surface antigen and/or DNA positive
• HCV RNA positive (an isolated positive HCV Ab is not an exclusion)
• 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 for >6 months (defined as the upper limit of normal at the reference laboratory)
• Significant hepatic fibrosis on screening elastography (Fibroscan value ≥8kPa; equates to >F2 fibrosis on the Metavir staging system)
• Primary Focal Segmental Glomerulosclerosis (FSGS), FSGS recurring in prior transplant, or other disease process at high risk of early graft failure due to renal disease recurrence per the treating transplant nephrologist
• Current use of amiodarone (due to interaction with sofosbuvir) for more than 3 months
• 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 of any investigational agent or approved medication, or participation in another kind interventional study that the responsible investigator deems to be an exclusion from period 6 months prior to screening to last study visit

Study findings are not yet available.