Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From HCV-Infected Donors to Uninfected Recipients
- Conditions
- HCV
- Interventions
- Other: Prophylaxis (P2W)Other: Transmit and Treat (T&T)
- Registration Number
- NCT05653232
- Lead Sponsor
- Johns Hopkins University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- Participant meets the standard criteria for KT at local center.
- Participant is able to understand and provide informed consent.
- Participant is ≥ 18 years old.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prophylaxis (P2W) Prophylaxis (P2W) Prophylaxis is one dose of sofosbuvir/velpatasvir (SOF/VEL) pre-HCV D+/R- kidney transplant (KT), continued for 2 weeks. Transmit and Treat (T&T) Transmit and Treat (T&T) T\&T is study-supplied SOF/VEL for 12 weeks starting on post-HCV D+/R- kidney transplant day participant's insurance approves standard of care DAAs, or post-KT day 14, whichever comes first.
- Primary Outcome Measures
Name Time Method Composite event of HCV-related or HCV treatment-related death, fibrosing cholestatic hepatitis, or HCV relapse Within 26 weeks of transplant Proportion of events in each arm.
Number of participants with liver injury The first 28 days post-transplant Measured with a longitudinal model of Alanine aminotransferase (ALT).
- Secondary Outcome Measures
Name Time Method Participant survival At 6 months and 1 year post-transplant Time to event (death)
Graft survival At 6 months and 1 year post-transplant Time to event (graft loss)
HCV plasma RNA At week 26 post-transplant Based on local testing
Graft rejection At 6 months and 1 year post-transplant Cumulative incidence of rejection
Graft function - eGFR <60 Months 3, 6, 9, and 12 post-transplant Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) \< 60 mL/min/1.73 m2
Incidence and severity of bacterial, fungal, viral, and opportunistic infections From transplant through end of follow up (at least 6 months, up to 3 years post-transplant) Cumulative incidence of infections
Prevalence of donor specific antibody (DSA) At 4 weeks and 6 months post-transplant, and with any episode of clinically suspected or proven rejection. Proportion of participants with a de novo donor-specific human leukocyte antigen (HLA) antibody as measured and reported by local sites' lab
Graft function - eGFR slope Months 3, 6, 9, and 12 post-transplant The slope of eGFR by CKD-EPI, over time based on serum creatinine
Development of HCV resistance-associated variants (RAVs) With any HCV viremia after P2W or T&T through end of follow up (at least 6 months, up to 3 years post-transplant) Proportion of participants with RAVs as measured and reported by local sites' lab
Incidence of surgical and vascular complications During the first year post-transplant Number of surgical and vascular complications
Graft function - mean eGFR Months 3, 6, 9, and 12 post-transplant Mean calculated eGFR by CKD-EPI
Trial Locations
- Locations (7)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
University of Wisconsin, Madison
🇺🇸Madison, Wisconsin, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
NYU Langone Health
🇺🇸New York, New York, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Utah Medical Center
🇺🇸Salt Lake City, Utah, United States