The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

July 18, 2023 updated by: Amit D Tevar, MD

Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)

This is an open-label, pilot trial to test the safety and efficacy of transplantation of kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney transplant waitlist. Treatment and prophylaxis will be administered using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Detailed Description

This is a prospective, single center, pilot, open-label study of transplantation of kidneys of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor HCV by measuring HCV RNA in renal transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy.

Recipients of a kidney from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for evidence of transmission.

To be eligible for the study, subjects need to be listed for renal transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria (recipients):

  1. Patients with end-stage renal disease listed for kidney transplantation at UPMC.
  2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min
  3. Age ≥ 18
  4. No available living kidney donor
  5. Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time
  6. Have panel reactive antibody level of <98%
  7. No obvious contraindication to kidney transplant
  8. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
  9. Able to provide informed consent
  10. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

  1. HIV positive
  2. HCVAb or HCV RNA positive
  3. Presence of behavioral risk factors for contracting HCV other than being on hemodialysis. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.
  4. Hepatitis B surface antigen positive
  5. History of liver cirrhosis
  6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months
  7. History of atrial fibrillation requiring the use of amiodarone over the past 12m
  8. Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team
  9. Receipt of prior organ transplant
  10. Waitlisted for a multi-organ transplant
  11. Pregnant women
  12. Known allergy to sofosbuvir/velpatasvir
  13. Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Inclusion criteria (donors):

  1. HCV antibody positive
  2. HCV NAT negative or positive
  3. Kidney donor profile index (KDPI) score <85

Exclusion criteria (donors):

  1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)
  2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)
  3. Known ongoing therapy for HCV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor

Kidney recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated.

Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

12-week, oral, fixed-dose
Other Names:
  • Epclusa
Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor
Starting post-operative day 1, kidney recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).
12-week, oral, fixed-dose
Other Names:
  • Epclusa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 5 years
Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group
5 years
HCV free at 1 year
Time Frame: 1 year
Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
All-cause mortality
Time Frame: 5 years
5 years
Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
Time Frame: 5 years
5 years
Incidence of allograft rejection
Time Frame: 5 years
5 years
Incidence of graft loss
Time Frame: 5 years
5 years
Waitlist time after enrollment
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Amit Tevar, MD, University of Pittsburgh
  • Study Director: Fernanda Silviera, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2019

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

January 15, 2019

First Submitted That Met QC Criteria

January 15, 2019

First Posted (Actual)

January 18, 2019

Study Record Updates

Last Update Posted (Actual)

July 20, 2023

Last Update Submitted That Met QC Criteria

July 18, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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