Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From HCV-Infected Donors to Uninfected Recipients (PREVENT-HCV)

Prophylaxis With Direct-acting Antivirals for Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: a Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: HCV
• Intervention / Treatment: Other: Prophylaxis (P2W); Other: Transmit and Treat (T&T)

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christine Durand, MD; Phone Number: 410-955-5684; Email: cdurand2@jhmi.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California San Diego
      • Contact: Saima Aslam, MD; Email: saslam@ucsd.edu
      • Principal Investigator: Saima Aslam, MD
    • Loma Linda, California, United States, 92408
      • Recruiting
      • Loma Linda University health
      • Contact: Mina Rakoski, MD; Email: mrakoski@llu.edu
      • Principal Investigator: Mina Rakoski, MD
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins University
      • Contact: Christine Durand, MD; Phone Number: 410-955-5684; Email: cdurand2@jhmi.edu
      • Principal Investigator: Christine Durand, MD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Aprajita Mattoo, MD; Email: Aprajita.Matoo@nyulangone.org
      • Principal Investigator: Aprajita Mattoo, MD
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School Of Medicine At Mount Sinai
      • Contact: Susan Lerner, MD; Email: Susan.Lerner@mountsinai.org
      • Principal Investigator: Susan Lerner, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center
      • Principal Investigator: Fernanda Silveira, MD
      • Contact: Fernanda Silveira, MD; Email: silvfd@upmc.edu
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah Medical Center
      • Contact: Miklos Molnar, MD, PhD; Email: miklos.molnar@hsc.utah.edu
      • Principal Investigator: Miklos Molnar, MD, PhD
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Gaurav Gupta, MD; Email: gaurav.gupta@vcuhealth.org
      • Principal Investigator: Gaurav Gupta, MD
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Terminated
      • University of Wisconsin, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylaxis (P2W); Prophylaxis is one dose of sofosbuvir/velpatasvir (SOF/VEL) pre-HCV D+/R- kidney transplant (KT), continued for 2 weeks.	Other: Prophylaxis (P2W); For participants enrolled in P2W arm, the initial dose of SOF/VEL will be administered to the recipient when called to the operating room for transplant (typically 1-3 hours prior to the start of surgery). Post-transplant, SOF/VEL will be continued daily for 13 days post-KT (a total of 14 doses administered).
Experimental: 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.	Other: Transmit and Treat (T&T); For participants enrolled in T&T arm, SOF/VEL will begin between post-KT day 0 and post-KT day 14. Participants will be clinically-prescribed DAAs once viremia is detected, and participant's insurance will be petitioned to obtain treatment as soon as possible. If insurance-provided DAAs are approved before post-KT day 14, participant will begin 12 weeks of study-provided SOF/VEL on date of insurance-provided DAAs approval. If insurance-provided DAAs are not approved by post-KT day 14, study-provided SOF/VEL will begin on post-KT day 14 and continue for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite event of HCV-related or HCV treatment-related death, fibrosing cholestatic hepatitis, or HCV relapse	Proportion of events in each arm.	Within 26 weeks of transplant
Number of participants with liver injury	Measured with a longitudinal model of Alanine aminotransferase (ALT).	The first 28 days post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant survival	Time to event (death)	At 6 months and 1 year post-transplant
Graft survival	Time to event (graft loss)	At 6 months and 1 year post-transplant
HCV plasma RNA	Based on local testing	At week 26 post-transplant
Graft rejection	Cumulative incidence of rejection	At 6 months and 1 year post-transplant
Prevalence of donor specific antibody (DSA)	Proportion of participants with a de novo donor-specific human leukocyte antigen (HLA) antibody as measured and reported by local sites' lab	At 4 weeks and 6 months post-transplant, and with any episode of clinically suspected or proven rejection.
Graft function - eGFR <60	Proportion of participants with glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) < 60 mL/min/1.73 m2	Months 3, 6, 9, and 12 post-transplant
Graft function - mean eGFR	Mean calculated eGFR by CKD-EPI	Months 3, 6, 9, and 12 post-transplant
Graft function - eGFR slope	The slope of eGFR by CKD-EPI, over time based on serum creatinine	Months 3, 6, 9, and 12 post-transplant
Development of HCV resistance-associated variants (RAVs)	Proportion of participants with RAVs as measured and reported by local sites' lab	With any HCV viremia after P2W or T&T through end of follow up (at least 6 months, up to 3 years post-transplant)
Incidence of surgical and vascular complications	Number of surgical and vascular complications	During the first year post-transplant
Incidence and severity of bacterial, fungal, viral, and opportunistic infections	Cumulative incidence of infections	From transplant through end of follow up (at least 6 months, up to 3 years post-transplant)

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Christine Durand, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Public Health; Environment and Public Health; Complex Mixtures; Tars; Coal Tar; Disease Transmission, Infectious
• Other Study ID Numbers: IRB00316833; U01AI157931 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No