Lung Transplant HCV, Pilot Study

Early Phase 1

Active, not recruiting

• Conditions: Lung Transplant Infection; Hepatitis C
• Interventions: Drug: Sofosbuvir-velpatasvir (400 mg/100 mg); Device: Ex Vivo Lung Perfusion (EVLP)

• Registration Number: NCT03112044
• Lead Sponsor: University Health Network, Toronto

Brief Summary

In this study HCV negative recipients will be transplanted with HCV positive lungs. Investigators will attempt to decrease infectivity rates by performing Normothermic Ex vivo Lung Perfusion (EVLP), which is an approved method of donor lung preservation, assessment and treatment, and could be an excellent platform to reduce/eliminate hepatitis C virus. Patients will be treated by the standard approved direct-acting antivirals (DAAs) if infection occurs. It is planned to enroll 20 patients from the Lung transplant wait list in this study. Patients will be actively followed for 6 months including HCV PCR tests and then for up for 5 years to look for evidence of HCV infection and any liver or extra-hepatic complications, as well as standard post-transplant complications. This will be a single center pilot study.

Detailed Description

The success of lung transplantation (LTx) is significantly hindered by the lack of sufficient number of available donors. Many potential donor lungs cannot be utilized in clinical transplantation because donors have chronic viral infections such as hepatitis C (HCV) infection. This study will test the possibility of safely transplanting lungs from HCV positive donors. Donor lungs will be subjected to Normothermic Ex vivo Lung Perfusion (EVLP) for 6 hours for organ assessment and reduction of viral load prior to transplantation. After transplantation, recipients will be carefully monitored for HCV infection and if infection occurs, they will be promptly treated with highly effective antiviral therapy using newly approved DAAs. The aim of the study is to show that transplantation of lungs from HCV positive donors is safe in the era of DAAs. The hypothesis is that the rate of HCV transmission to recipients will be lower than previously described due to EVLP pre-treatment and any HCV transmission that does occur will be readily treatable and curable. If successful, the knowledge from this study can have a large impact to patients with end stage organ diseases by providing a large novel source of donors for lung and potentially other organ transplantations.

Study Timeline

• Study First Submitted: 2017-04-06
• Study First Submitted QC: 2017-04-11
• Study First Posted: 2017-04-13
• Study Start: 2017-09-19
• Primary Completion: 2020-01-02
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Recipients listed for single or bilateral lung transplant
• HCV Nucleic Acid Amplification Testing (NAT) negative
• Ability to provide written informed consent

Exclusion Criteria

• Participation in another interventional clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HCV+ lung transplant to HCV- recipients	Sofosbuvir-velpatasvir (400 mg/100 mg)	HCV+ donor lungs will be treated with Normothermic Ex Vivo Lung Perfusion (EVLP) in order to reduce viral load and minimize risk of HCV transmission. Patients who become viremic defined as at least two consecutive positive samples will receive sofosbuvir/velpatasvir 400 mg/100 mg (Epclusa) for 12 weeks.
HCV+ lung transplant to HCV- recipients	Ex Vivo Lung Perfusion (EVLP)	HCV+ donor lungs will be treated with Normothermic Ex Vivo Lung Perfusion (EVLP) in order to reduce viral load and minimize risk of HCV transmission. Patients who become viremic defined as at least two consecutive positive samples will receive sofosbuvir/velpatasvir 400 mg/100 mg (Epclusa) for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Safety of transplantation from HCV positive donors to HCV negative recipients	6 months	Safety of transplantation using HCV positive donors reflected by 6 month survival and being free of HCV by PCR (either due to lack of transmission or as a result of treatment).

Secondary Outcome Measures

Name	Time	Method
Incidence of HCV transmission	6 months	Incidence of donor to recipient HCV transmission.
Time to viremia development	6 months	Interval of time from transplantation to development of viremia
HCV cure rates	6 months	HCV cure rates after treatment of infected patients
Correlation between viral loads and recipient infection	6 months	Correlation between donor viremia, EVLP perfusate virus load (PCR), lung tissue virus load at the end of EVLP (PCR) and recipient infection

Trial Locations

Locations (1)

University Health Network Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada