Lung Transplant HCV, Pilot Study

NCT ID: NCT03112044

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-19
• Study Completion Date: 2026-05-31

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.

Conditions

Lung Transplant Infection; Hepatitis C

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HCV+ lung transplant to HCV- recipients

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.

Group Type: EXPERIMENTAL

Sofosbuvir-velpatasvir (400 mg/100 mg)

Intervention Type: DRUG

Patients will have standard monitoring with HCV RNA and liver panel assessment at 2 week intervals until HCV is undetectable and then at the end of treatment and 3 and 6 months following its completion. Post-operative transplant care and immunosuppression will be carried on as usual transplant practice at Toronto General Hospital.

Ex Vivo Lung Perfusion (EVLP)

Intervention Type: DEVICE

Normothermic EVLP is a method of donor lung preservation, assessment, treatment, and repair of injured organs. This method allows donor lungs to be treated for at least 12h under protective physiological conditions.

Interventions

Sofosbuvir-velpatasvir (400 mg/100 mg)

Patients will have standard monitoring with HCV RNA and liver panel assessment at 2 week intervals until HCV is undetectable and then at the end of treatment and 3 and 6 months following its completion. Post-operative transplant care and immunosuppression will be carried on as usual transplant practice at Toronto General Hospital.

Intervention Type: DRUG

Ex Vivo Lung Perfusion (EVLP)

Normothermic EVLP is a method of donor lung preservation, assessment, treatment, and repair of injured organs. This method allows donor lungs to be treated for at least 12h under protective physiological conditions.

Intervention Type: DEVICE

Other Intervention Names

Epclusa; Normothermic EVLP

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcelo Cypel, MD MSc FRCSC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

University Health Network Toronto General Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Cypel M, Feld JJ, Galasso M, Pinto Ribeiro RV, Marks N, Kuczynski M, Kumar D, Bahinskaya I, Bagnato VS, Kurachi C, Slutsky AS, Yeung JC, Donahoe L, de Perrot M, Yasufuku K, Pierre A, Binnie M, Chaparro C, Martinu T, Chen M, Tikkanen J, Chow CW, Sidhu A, Waddell TK, Keshavjee S, Singer LG, Humar A. Prevention of viral transmission during lung transplantation with hepatitis C-viraemic donors: an open-label, single-centre, pilot trial. Lancet Respir Med. 2020 Feb;8(2):192-201. doi: 10.1016/S2213-2600(19)30268-1. Epub 2019 Oct 9.

Reference Type: DERIVED

PMID: 31606437 (View on PubMed)

Other Identifiers

UHNTID006

Identifier Type: OTHER

Identifier Source: secondary_id

16-6084

Identifier Type: -

Identifier Source: org_study_id