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

Sponsor
Amit D Tevar, MD (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03809533
Collaborator
University of Pittsburgh Medical Center (Other)
30
1
2
59.1
0.5

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)
Actual Study Start Date :
May 29, 2019
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

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).

Drug: sofosbuvir/velpatasvir
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).

    Drug: sofosbuvir/velpatasvir
    12-week, oral, fixed-dose
    Other Names:
  • Epclusa
  • Outcome Measures

    Primary Outcome Measures

    1. Adverse Events [5 years]

      Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

    2. HCV free at 1 year [1 year]

      Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

    Secondary Outcome Measures

    1. Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients [5 years]

    2. Incidence of allograft rejection [5 years]

    3. Incidence of graft loss [5 years]

    4. All-cause mortality [5 years]

    5. Waitlist time after enrollment [5 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UPMC Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • Amit D Tevar, MD
    • University of Pittsburgh Medical Center

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Amit D Tevar, MD, Associate Professor of Surgery, University of Pittsburgh
    ClinicalTrials.gov Identifier:
    NCT03809533
    Other Study ID Numbers:
    • STUDY19100135
    First Posted:
    Jan 18, 2019
    Last Update Posted:
    Oct 29, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 29, 2021