HCV
Conditions
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.
Interventions
OTHERProphylaxis (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).
OTHERTransmit 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.
Sponsors
Johns Hopkins University
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 <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 |
| Graft function - mean eGFR | Months 3, 6, 9, and 12 post-transplant | Mean calculated eGFR by CKD-EPI |
| 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 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 |
| Incidence of surgical and vascular complications | During the first year post-transplant | Number of surgical and vascular complications |
Countries
United States
Contacts
CONTACTChristine Durand, MD
PRINCIPAL_INVESTIGATORChristine Durand, MD
Johns Hopkins University
Outcome results
None listed