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The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03819322
Recruitment Status : Active, not recruiting
First Posted : January 28, 2019
Last Update Posted : October 6, 2021
Sponsor:
Collaborator:
University of Pittsburgh Medical Center
Information provided by (Responsible Party):
Naudia Jonassaint, University of Pittsburgh

Study Description
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Brief Summary:
This is an open-label, pilot trial to test the safety and efficacy of transplantation of livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver 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
Liver Transplant Hepatitis C Drug: sofosbuvir/velpatasvir Phase 2

Detailed Description:

This is a prospective, single center, pilot, open-label study of transplantation of livers of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor transmission of HCV by measuring HCV RNA in liver 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 liver 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 liver transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 73 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transplantation of Livers of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa®)
Actual Study Start Date : August 15, 2019
Estimated Primary Completion Date : May 1, 2024
Estimated Study Completion Date : May 1, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arms and Interventions
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Arm Intervention/treatment
Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor

Liver 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 Name: Epclusa
Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor
Post-operative day 1, liver 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 Name: Epclusa


Outcome Measures
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Primary Outcome Measures :
  1. Adverse events [ Time Frame: 5 years ]
    Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group

  2. 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


Secondary Outcome Measures :
  1. Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients [ Time Frame: 5 years ]
  2. Incidence of allograft rejection [ Time Frame: 5 years ]
  3. Incidence of graft loss [ Time Frame: 5 years ]
  4. All-cause mortality [ Time Frame: 5 years ]
  5. Waitlist time after enrollment [ Time Frame: 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria (recipients):

  1. Patients with end-stage liver disease listed for liver transplantation at UPMC.
  2. Age ≥ 18
  3. No available living liver donor
  4. Listed for an isolated liver transplant at UPMC
  5. Have panel reactive antibody level of <98%
  6. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
  7. Able to provide informed consent
  8. 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. 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 atrial fibrillation requiring the use of amiodarone over the past 12m
  6. Receipt of prior organ transplant
  7. Waitlisted for a multi-organ transplant
  8. Pregnant women
  9. Known allergy to sofosbuvir/velpatasvir
  10. 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

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03819322


Locations
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United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Naudia Jonassaint
University of Pittsburgh Medical Center
Investigators
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Study Director: Fernanda Silviera, MD University of Pittsburgh
Principal Investigator: Naudia Jonassaint, MD University of Pittsburgh
More Information
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Responsible Party: Naudia Jonassaint, Assistant Professor of Medicine and Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03819322    
Other Study ID Numbers: STUDY19100082
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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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:
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Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
 Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Flaviviridae Infections
Sofosbuvir
Velpatasvir
Antiviral Agents
Anti-Infective Agents