Clinical trial NCT04075916: A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients
Official title: A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: End Stage Renal Disease
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-09-03
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Post-treatment sustained virologic response (SVR) to direct-acting antiviral (DAA)
timeFrame: Baseline to 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital/University of Miami
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: New York Presbyterian Hospital/Columbia University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: University of Pennsylvania
name: Peter Reese, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: