Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR

February 17, 2020 updated by: University of Florida
It is well recognized that a subset of patients who contracts Hepatitis C virus (HCV) spontaneously clears the virus. Such individuals are anti-HCV antibody positive, yet HCV RNA PCR negative in the blood. While they have not been considered candidates for live kidney donation in the past, with the recent availability of novel anti-HCV drugs with >95% cure rates, they now represent a potential pool of donor candidates, especially since the risk for transmission of HCV to the recipient is extremely low. The investigators goal is to demonstrate that live kidney donation from anti-HCV positive, HCV RNA PCR negative individuals is safe and carries a negligible risk of viral transmission to the recipient.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Individuals who test positive for anti-HCV IgG antibody, but who have negative blood HCV RNA PCR are generally considered to have been infected with HCV but to have cleared the the virus spontaneously. However, due to the general conservative approach of living donor kidney transplant programs, these individuals are not considered potential live kidney donors, despite being considered at extremely low risk for HCV transmission to the recipient. This reluctance stems from past experiences with post-transplant HCV complications, both hepatic (e.g. cirrhosis) and extra-hepatic (e.g. transplant glomerulonephritis) and from the fact that the historical mainstay of HCV treatment, interferon, was poorly tolerated, had low cure rates, and caused transplant rejection. Now, however, highly effective novel therapeutics may transform the way transplant physicians and patients think about HCV-positive donated kidneys.

With these new agents, the current cure rates for HCV now exceed 95%. A recent report demonstrated high cure rates even in the liver transplant setting, suggesting that immunosuppression does not impede eradication and that interactions between HCV and transplant drugs can be successfully managed. Thus, while the risk of transmission of infection from anti-HCV antibody positive, HCV PCR-negative is not known, if transmission were to occur, treatment is now possible, to the point where transplant professionals are beginning to advocate using anti-HCV Ab positive individuals as donors for HCV-negative recipients. A group in Barcelona reported transplantation of a live donor kidney from a donor treated with an anti-HCV regimen that achieved a sustained virological response to her spouse with no transmission of infection.

The main area of concern seems to be what is described as "occult HCV infection"- the presence of HCV RNA in peripheral blood mononuclear cells and organ tissue by ultrasensitive assays in the absence of detectable RNA in the serum. However, this entity is itself controversial, and its significance is uncertain, with inadequately described risk of transmission. If HCV were transmitted and successfully treated, another concern is the potential residual risks of viral complications, even though these have not been evident in any previous trials. Finally, a major concern is financial, as HCV treatment currently costs more than $80,000 for a 3-month regimen. However, chronic hemodialysis costs upwards of $100,000 per year when all costs are considered, while kidney transplantation costs only about $20,000 per year after the first year. Thus, over time, even after treatment for CMV infection, if it is required, kidney transplantation would result in an overall cost savings to the health care system.

Given the unknown, though generally considered very low risk of transmission of HCV from an antibody-positive, PCR-negative individual, combined with the wide availability of effective treatment for HCV infection, it is felt that the recipient is not exposed to a high risk of infection in such a transplant. Furthermore, this small risk needs to be weighed against the risk of staying on dialysis, which carries a mortality rate of 6.5-7.4 times that of the general population and 4.6-5.9 times that of the renal transplant population. The case becomes even more compelling when considering patients with a high risk of deterioration if they continue dialysis (elderly, diabetics, and those with cardiovascular disease), disadvantageous blood types, and those with broad sensitization, with extremely limited compatible donor options. Given the proven survival benefit of kidney transplantation in patients with chronic HCV, there is ample reason to believe that providing HCV positive kidneys and HCV therapy (if indeed required) to HCV negative recipients will lead to better outcomes than those associated with remaining on dialysis.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Not Applicable

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

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • Shands at the University of Florida

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 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Donor inclusion criteria:

  • The donor candidate must be anti-HCV positive by ELISA and HCV RNA negative by PCR, with both tests repeated for confirmation, as per standard protocol.
  • The donor must be evaluated and cleared by Hepatology, which is currently the standard of care for HCV seropositive individuals.
  • The donor must meet criteria for living kidney donation and be approved by the UF Health Shands Kidney Transplant Medical Review Board.

Recipient inclusion criteria:

  • The recipient may be HCV antibody negative or anti-HCV antibody positive but HCV RNA negative by PCR.
  • The recipient must meet the criteria for kidney transplantation and be approved by the UF Health Kidney Transplant Program Medical Review Board.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study Arm
Donor candidates with their intended recipients who meet criteria will be enrolled into this, the sole arm of our study. Donor-recipient pairs will be screened to meet criteria, and will proceed to kidney transplantation and post-transplant monitoring
Procedure: Kidney transplantation
Once the donor and recipient candidates have met inclusion criteria and cleared study-specific as well as standard of care screening, they will proceed to live-donor kidney transplantation and subsequent post-transplant monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maintenance of HCV seronegativity
Time Frame: 3 months
At 3 months post-transplant, recipients will be screened for HCV seropositivity. A negative seropositive result will conclude the recipient's participation in the study
3 months

Collaborators and Investigators

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

Sponsor

University of Florida

Investigators

  • Principal Investigator: Karl Womer, MD, Univesity of Florida

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.

General Publications

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

March 1, 2016

Primary Completion (Actual)

February 1, 2020

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

January 27, 2016

First Submitted That Met QC Criteria

January 29, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

February 19, 2020

Last Update Submitted That Met QC Criteria

February 17, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB201500543

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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.

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