Clinical trial NCT05653232: Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From HCV-Infected Donors to Uninfected Recipients
Official title: Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: HCV
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-12-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being done to find out the best time to start medication for Hepatitis C Virus (HCV) in HCV-negative recipients of HCV-positive (HCV D+/R-) kidney transplants. Participants will be randomized into one of two groups:

Arm 1 - Prophylaxis: This group will start the HCV medication before transplant and will take a shorter course of HCV medication for 2 weeks.

Arm 2 - Transmit and Treat: This group will start the HCV medication after transplant and will take the full course (12 weeks) of HCV medication.

Detailed description: In the past, HCV-positive (HCV+) kidneys were not given to HCV-negative recipients. But over the last few years, medications have been created that cure HCV in nearly 100% of patients. HCV+ transplants to HCV-negative recipients have become increasingly common now that HCV can be cured.

There are two approaches to giving HCV medication to recipients of these transplants. The first is a prophylaxis approach. With prophylaxis, HCV medication is started before transplant and continued for a shorter course after transplant. The second is a transmit-and-treat approach. With transmit-and-treat, HCV medication is started after transplant and continued for the full, recommended course. Both approaches have successfully cured HCV in HCV-negative recipients of HCV+ organs.

This research will use a study drug called sofosbuvir/velpatasvir (SOF/VEL). It contains two drugs for treating HCV in one pill. We will compare giving SOF/VEL for 2 weeks starting pre-transplant (prophylaxis) to giving SOF/VEL for 12 weeks starting no later than 14 days post-transplant (transmit-and-treat).

SOF/VEL belongs to a group of medications called direct-acting antiviral agents (DAAs). These drugs prevent HCV from multiplying and spreading in the human body. SOF/VEL are already approved and used for 12 weeks to treat HCV infection. The use of SOF/VEL for 2 weeks in preventing HCV infection has not been studied. The FDA is allowing SOF/VEL to be used in this study.

Eligibility criteria: Inclusion Criteria:

* Participant meets the standard criteria for KT at local center.
* Participant is able to understand and provide informed consent.
* Participant is ≥ 18 years old.

Exclusion Criteria:

* Participant has active HCV infection (detectable HCV RNA) at time of screening.
* Participant has cirrhosis or advanced liver fibrosis.
* Participant's aspartate aminotransferase (AST) or ALT \> 2.5 times the upper limit of normal (ULN), within 60 days of screen.
* Participant has human immunodeficiency virus infection (HIV), or active hepatitis B (HBV) infection.
* Participant is unable to safely substitute or discontinue a medication that is contraindicated with the study medication.
* Past or current medical problems, which may pose additional risks from participation in the study, interfere with the participant's ability to comply with study, or impact the quality of the data obtained from the study.
* Participant is pregnant or breastfeeding.

Primary outcomes:
measure: Composite event of HCV-related or HCV treatment-related death, fibrosing cholestatic hepatitis, or HCV relapse
timeFrame: Within 26 weeks of transplant
measure: Number of participants with liver injury
timeFrame: The first 28 days post-transplant
Secondary outcomes:
measure: Participant survival
timeFrame: At 6 months and 1 year post-transplant
measure: Graft survival
timeFrame: At 6 months and 1 year post-transplant
measure: HCV plasma RNA
timeFrame: At week 26 post-transplant
measure: Graft rejection
timeFrame: At 6 months and 1 year post-transplant
measure: Prevalence of donor specific antibody (DSA)
timeFrame: At 4 weeks and 6 months post-transplant, and with any episode of clinically suspected or proven rejection.
measure: Graft function - eGFR <60
timeFrame: Months 3, 6, 9, and 12 post-transplant
measure: Graft function - mean eGFR
timeFrame: Months 3, 6, 9, and 12 post-transplant
measure: Graft function - eGFR slope
timeFrame: Months 3, 6, 9, and 12 post-transplant
measure: Development of HCV resistance-associated variants (RAVs)
timeFrame: With any HCV viremia after P2W or T&T through end of follow up (at least 6 months, up to 3 years post-transplant)
measure: Incidence and severity of bacterial, fungal, viral, and opportunistic infections
timeFrame: From transplant through end of follow up (at least 6 months, up to 3 years post-transplant)
measure: Incidence of surgical and vascular complications
timeFrame: During the first year post-transplant
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin, Madison
state: Wisconsin
Study officials:
affiliation: Johns Hopkins University
name: Christine Durand, MD
role: PRINCIPAL_INVESTIGATOR
References: