Transplanting Hepatitis C Positive Organs

Study Overview
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Brief Summary
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This is an open-label, pilot safety and efficacy trial for adults who are active on the heart, lung, or kidney transplantation lists and are eligible to receive an organ from an increased risk donor who has evidence of active or prior hepatitis C infection (HCV).

Detailed Description
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This is an open label pilot study transplanting organs from Hepatitis C positive donors into HCV uninfected recipients at Brigham and Women's Hospital. Heart, lung and kidney transplant participants will be stratified into two different study arms depending on whether the donor of the organ was HCV nucleic acid amplifications technology (NAT) positive or negative. In the NAT positive arm, the recipients will receive a course of direct acting antivirals (DAA) to begin on the day of transplant. If the donor was HCV antibody (Ab) positive and NAT negative, the recipients will receive close monitoring with serial HCV viral loads (VL) and will only begin treatment with DAA if they develop HCV viremia.

Official Title
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Transplanting Organs From Hepatitis C Positive Donors to Hepatitis C Uninfected Recipients

Conditions
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Hepatitis C, Awaiting Organ Transplant

Intervention / Treatment
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* Drug: Sofosbuvir/velpatasvir
* Other: Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women who are age ≥ 18 years Active on either the cardiac, lung, or kidney transplant waiting list Willing and able to provide written informed consent to receive organs from an increased risk donor with a known transmissible infection Exclusion Criteria: Hepatitis B NAT or viral load positive Evidence of cirrhosis or clinically significant liver disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCV NAT Positive Donor<br>Intervention: 2 week treatment course with a direct acting antiviral, sofosbuvir 400mg / velpatasvir 100mg daily Participants who receive allografts from a donor who is HCV NAT positive will receive treatment with a direct acting antiviral, sofosbuvir 400mg / velpatasvir 100mg daily, beginning on the day of transplant. | Drug: Sofosbuvir/velpatasvir<br>* 2 weeks of treatment beginning on the day of transplant<br>* Other names: Epclusa;|
| Experimental: HCV NAT Negative, HCV Ab Positive Donor<br>Intervention: HCV viral load monitoring Participants who receive allografts from a donor who is HCV Ab positive and NAT negative will have close serial HCV viral load monitoring and will be treated with a direct acting antiviral, 400mg / velpatasvir 100mg daily, for 6 weeks if HCV viremia develops. | Drug: Sofosbuvir/velpatasvir<br>* 2 weeks of treatment beginning on the day of transplant<br>* Other names: Epclusa;Other: Monitoring<br>* Close HCV viral load monitoring Will receive direct acting antiviral treatment with 6 weeks of sofosbuvir/velpatasvir if the recipient develops HCV viremia during the post-transplant HCV viral load testing<br>* Other names: Sofosbuvir/velpatasvir (Epclusa);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft survival | Functioning allograft not requiring mechanical support | 6 months post-transplant | 
| HCV status of the transplant recipient | Sustained virologic response (SVR) 12 weeks after HCV treatment completion in Arm A or at 6 months in Arm B (SVR defined as HCV RNA < lower limit of quantification) | 6 months post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related adverse events | Number of treatment related adverse events per patient using direct-acting antiviral HCV regimens in post transplant recipients | 6 months post-transplant |