Transplanting Hepatitis C Positive Organs

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

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).

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C; Awaiting Organ Transplant
• Intervention / Treatment: Drug: Sofosbuvir/velpatasvir; Other: Monitoring

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 148
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ann Woolley, MD; Phone Number: 617-732-5500; Email: awoolley@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Ann Woolley, MD; Phone Number: 617-525-8418; Email: awoolley@partners.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCV NAT Positive Donor; 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; 2 weeks of treatment beginning on the day of transplant; Other Names: Epclusa
Experimental: HCV NAT Negative, HCV Ab Positive Donor; 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; 2 weeks of treatment beginning on the day of transplant; Other Names: Epclusa; Other: Monitoring; 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; Other Names: Sofosbuvir/velpatasvir (Epclusa)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Lindsey Baden, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Woolley AE, Singh SK, Goldberg HJ, Mallidi HR, Givertz MM, Mehra MR, Coppolino A, Kusztos AE, Johnson ME, Chen K, Haddad EA, Fanikos J, Harrington DP, Camp PC, Baden LR; DONATE HCV Trial Team. Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients. N Engl J Med. 2019 Apr 25;380(17):1606-1617. doi: 10.1056/NEJMoa1812406. Epub 2019 Apr 3.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: 2016-P001170

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No