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

NCT ID: NCT05653232

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-19
• Study Completion Date: 2027-03-31

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.

Conditions

HCV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prophylaxis (P2W)

Prophylaxis is one dose of sofosbuvir/velpatasvir (SOF/VEL) pre-HCV D+/R- kidney transplant (KT), continued for 2 weeks.

Group Type: EXPERIMENTAL

Prophylaxis (P2W)

Intervention Type: OTHER

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).

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.

Group Type: EXPERIMENTAL

Transmit and Treat (T&T)

Intervention Type: OTHER

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.

Interventions

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).

Intervention Type: 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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine Durand, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

University of California San Diego

La Jolla, California, United States

Site Status: RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

NYU Langone Health

New York, New York, United States

Site Status: RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

University of Utah Medical Center

Salt Lake City, Utah, United States

Site Status: RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status: RECRUITING

University of Wisconsin, Madison

Madison, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Christine Durand, MD

Role: CONTACT

cdurand2@jhmi.edu

410-955-5684

Facility Contacts

Saima Aslam, MD

Role: primary

saslam@ucsd.edu

Christine Durand, MD

Role: primary

cdurand2@jhmi.edu

410-955-5684

Aprajita Mattoo, MD

Role: primary

Aprajita.Matoo@nyulangone.org

Susan Lerner, MD

Role: primary

Susan.Lerner@mountsinai.org

Miklos Molnar, MD, PhD

Role: primary

miklos.molnar@hsc.utah.edu

Gaurav Gupta, MD

Role: primary

gaurav.gupta@vcuhealth.org

Jacqueline Garonzik Wang, MD, PhD

Role: primary

garonzikwang@surgery.wisc.edu

Other Identifiers

U01AI157931

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00316833

Identifier Type: -

Identifier Source: org_study_id