Hepatitis C Positive Donor Into Hepatitis C Negative Recipients

May 4, 2023 updated by: University of Maryland, Baltimore

An Open-label Pilot Study to Determine the Safety and Efficacy of Hepatitis C Uninfected Recipients of Renal and Liver Transplants From a Currently Infected or Previously Infected Hepatitis C Donor

Despite many efforts to increase the size of the donor pool, there is a large and growing disparity between the number of donor kidneys and livers available for transplantation and the number of patients on the transplant waiting list. New donor pools are needed to satisfy the lack of available donor organs, along with expanded criteria for the existing donor pools.

A new standard of care now exists at most local and regional transplant centers. This new standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure rates and minimal side effect profiles. The efficacy and tolerability of these medications has allowed the expansion of the available donor pool by making HCV antibody positive non viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool may decrease time on the waiting list and improve quality of life and survival while waiting for organ transplantation.

Study Aim:

We propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ donors for transplantation into HCV negative recipients.

The primary purpose of the clinical protocol is to:

Collect prospective standard of care laboratory data on the results of these interventions

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Once the donor is accepted for transplantation and the recipient enrolled in the innovative clinical practice, donor HCV Ab status will be requested to initiate HCV RNA viral load testing.

Donor data will be recorded as per our standard practice and as mandated by UNOS. Our University of Maryland Medical Center team will be responsible for the donor operation as per standard of care.

Hep C Ab + NAT - Donor to Naïve Recipient This group will be monitored as illustrated in figure 1. Hep C Ab+ NAT+ Donor to Naïve Recipient HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.

Due to risk of HBV reactivation with DAA therapy, Hepatitis B surface antigen, surface antibody and core antibody status will be determined prior to HCV therapy. In patients with a prior exposure to HBV (i.e. positive HBV core antibody), Hepatitis B surface antigen levels will be monitored throughout therapy.

All patients will be seen in the Hepatology clinic within 4 weeks of transplant to establish care and follow-up.

HCV Therapy DAA therapy will be prescribed to all patients according to AASLD and IDSA joint guidelines, after giving consideration to the transplanted organ, renal function, and HCV genotype. All regimens exclude administration of ribavirin.

Therapy will be initiated as soon as possible (pending initiation of oral intake and insurance approval) following organ transplantation.

DAAs will be prescribed, after which medications will then be delivered to the patient's home or to the bedside.

If therapy is delayed beyond the 4-week appointment with Hepatology post-transplant, a protocol to monitor for infection, new-onset diabetes mellitus, glomerulonephritis and severe cholestatic hepatitis will be implemented. This protocol will include weekly blood work to include: CBC with differential, hepatic function panel, basic metabolic panel, and coagulation studies.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30 HCV Follow-Up HCV RNA, complete blood count (CBC) and liver biochemistries will be checked 4 weeks, 8 weeks, and 12 weeks after starting therapy. In patients previously exposed to HBV, HBV surface antigen will be followed qualitatively at the same intervals.

HCV RNA will also be checked 12 weeks after completion of therapy to define cure, or sustained virologic response. As part of long-term follow-up, HCV RNA will be checked annually at routine post-transplant visits.

If SVR is not achieved, a second, and if needed, third antiviral regimen will be provided to the participant at no cost.

Transplant, Post-Operative, Immunosuppression Follow Up All will be as per UMMC standard of care. Unless otherwise contraindicated, tacrolimus immune suppression will be favored, due to drug-drug interactions associated with DATs and cyclosporine.

Study Type

Interventional

Phase

  • Early Phase 1

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

    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center

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

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • RECIPIENT INCLUSION CRITERIA

    • Patients undergoing solid organ transplantation, including liver, kidney, and simultaneous liver-kidney who are not chronically infected with HCV
    • No evident contraindication for organ transplantation
    • HCV RNA negative (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
    • Age 18-75 years at the time of transplantation
    • Signed Informed Consent Form
    • No identified living organ donor
    • Able to travel to the University of Maryland for routine post-transplant and HCV follow-up visits
    • Men and women must agree to use at least one barrier method to prevent any secretion exchange
    • No active illicit drug use

DONOR INCLUSION CRITERIA

• Qualitative HCV nucleic acid test (NAT) positive and/or Hepatitis C antibody positive HCV donors offered to the University of Maryland.

Exclusion Criteria:

RECIPIENT EXCLUSION CRITERIA

  • History of prior solid organ transplantation
  • HIV infection
  • HBV surface antigen or DNA positive. Organs from HCV positive donors who are also Hepatitis B core antibody positive (hepatitis B surface antigen negative) can be used. These patients will however need to undergo prophylaxis for HBV according to their respective organ specific criteria and during treatment for hepatitis C due to the increased risk of reactivation of hepatitis B with DAA therapy
  • Waitlisted for a multi-organ transplant (with the exception of simultaneous liver-kidney transplant)
  • HCV RNA positive (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
  • Prior direct-acting antiviral (DAA) treatment for HCV. Patients previously treated with interferon-based regimens may be included.

DONOR EXCLUSION CRITERIA

  • Every donor that is considered unsuitable by the transplant surgeon for any reason.
  • Hepatocellular carcinoma
  • HIV infection
  • Use of HCV positive livers to be determined according to current existing criteria

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hep C Ab + NAT - Donor to Naïve Recipient

HCV Ab and HCV NAT testing at 3 days, week 1, week 2 and monthly for 3 months, at 6 months and 1 year. In approximately 16% of the patients, active hepatis C infection will ensue. For these patients, treatment is as follows.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30

Patients who are given organ transplants from donors that are Ab positive and NAT negative or Ab positive and NAT positive for Hepatitis C will be treated with direct acting antivirals after transplant if they become NAT+ for hepatitis C.

Interventions as follows.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30
Experimental: Hep C Ab+ NAT+ Donor to Naïve Recipient

HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is >1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30

Patients who are given organ transplants from donors that are Ab positive and NAT negative or Ab positive and NAT positive for Hepatitis C will be treated with direct acting antivirals after transplant if they become NAT+ for hepatitis C.

Interventions as follows.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30
Active Comparator: Hep C Ab- NAT - Donor to Naïve Recipient
Current standard of care for donor recipient infectious disease matching. No treatment necessary

Patients who are given organ transplants from donors that are Ab positive and NAT negative or Ab positive and NAT positive for Hepatitis C will be treated with direct acting antivirals after transplant if they become NAT+ for hepatitis C.

Interventions as follows.

Liver Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6
  • Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR>30
  • Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR>30

Kidney Transplant:

• Combinations of choice:

  • Mavyret (glecaprevir/pibrentasvir) - genotype 1-6
  • Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR>30

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SVR after receiving an organ from a donor previously exposed to Hepatitis C after treatment direct-acting antiviral drugs.
Time Frame: 12 months
To improve access to transplantation with use of HCV-non viremic and HCV-viremic organs in HCV negative patients
12 months

Collaborators and Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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)

July 1, 2019

Primary Completion (Actual)

July 1, 2019

Study Completion (Actual)

July 1, 2019

Study Registration Dates

First Submitted

October 8, 2018

First Submitted That Met QC Criteria

October 8, 2018

First Posted (Actual)

October 11, 2018

Study Record Updates

Last Update Posted (Estimate)

May 5, 2023

Last Update Submitted That Met QC Criteria

May 4, 2023

Last Verified

July 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Results will be published in peer reviewed journals.

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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.

Clinical Trials on Hepatitis C

Clinical Trials on Direct Acting Antivirals

3
Subscribe