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

HCV Clinical Trial

— PREVENT-HCV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05653232
• Other study ID #: IRB00316833
• Secondary ID: U01AI157931
• Status: Recruiting
• Phase: N/A
• Start date: April 19, 2023
• Est. completion date: March 2027

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Christine Durand, MD
• Phone: 410-955-5684
• Email: cdurand2[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 a Fibrosis-4 (FIB-4) score = 3.25 at time of screening, or a history of 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.

Related Conditions & MeSH terms

• HCV

Intervention

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).
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of California San Diego	La Jolla	California
United States	University of Wisconsin, Madison	Madison	Wisconsin
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah Medical Center	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with liver injury	Measured with a longitudinal model of Alanine aminotransferase (ALT).	The first 28 days post-transplant
Secondary	Participant survival	Time to event (death)	At 6 months and 1 year post-transplant
Secondary	Graft survival	Time to event (graft loss)	At 6 months and 1 year post-transplant
Secondary	HCV plasma RNA	Based on local testing	At week 26 post-transplant
Secondary	Graft rejection	Cumulative incidence of rejection	At 6 months and 1 year post-transplant
Secondary	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.
Secondary	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
Secondary	Graft function - mean eGFR	Mean calculated eGFR by CKD-EPI	Months 3, 6, 9, and 12 post-transplant
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Incidence of surgical and vascular complications	Number of surgical and vascular complications	During the first year post-transplant