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

End Stage Renal Disease Clinical Trial

— THINKER-NEXT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04075916
• Other study ID #: 10067385
• Secondary ID: U01DK126654
• Status: Recruiting
• Phase: Phase 2
• Start date: June 22, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: Peter Reese, MD, PhD
• Phone: (307) 22-THINK
• Email: thinker[@]med.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 1, 2025
• Est. primary completion date: May 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• End Stage Renal Disease
• Hepatitis
• Hepatitis C
• Kidney Failure, Chronic

Intervention

Drug:
• Epclusa
All patients will receive 12 weeks of sofosbuvir/velpatasvir as per the FDA label.

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Florida	Gainesville	Florida
United States	Jackson Memorial Hospital/University of Miami	Miami	Florida
United States	Vanderbilt University	Nashville	Tennessee
United States	New York Presbyterian Hospital/Columbia University	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-treatment sustained virologic response (SVR) to direct-acting antiviral (DAA)	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)	Baseline to 24 weeks