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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI157931 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prophylaxis (P2W) | Experimental | Prophylaxis is one dose of sofosbuvir/velpatasvir (SOF/VEL) pre-HCV D+/R- kidney transplant (KT), continued for 2 weeks. |
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| Transmit and Treat (T&T) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prophylaxis (P2W) | 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). |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christine Durand, MD | Contact | 410-955-5684 | cdurand2@jhmi.edu |
| Name | Affiliation | Role |
|---|---|---|
| Christine Durand, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego | Recruiting | La Jolla | California | 92037 | United States |
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| Transmit and Treat (T&T) | 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. |
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| 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 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) |
| Incidence of surgical and vascular complications | Number of surgical and vascular complications | During the first year post-transplant |
| Loma Linda University Health | Recruiting | Loma Linda | California | 92408 | United States |
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| Johns Hopkins University | Recruiting | Baltimore | Maryland | 21205 | United States |
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| NYU Langone Health | Recruiting | New York | New York | 10016 | United States |
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| Icahn School of Medicine at Mount Sinai | Recruiting | New York | New York | 10029 | United States |
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| University of Pittsburgh Medical Center | Recruiting | Pittsburgh | Pennsylvania | 15213 | United States |
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| University of Utah Medical Center | Recruiting | Salt Lake City | Utah | 84132 | United States |
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| Virginia Commonwealth University | Recruiting | Richmond | Virginia | 23298 | United States |
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| University of Wisconsin, Madison | Terminated | Madison | Wisconsin | 53792 | United States |
| ID | Term |
|---|---|
| D018562 | Disease Transmission, Infectious |
| D003033 | Coal Tar |
| ID | Term |
|---|---|
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D013638 | Tars |
| D045424 | Complex Mixtures |
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