Clinical trial NCT03112044: Lung Transplant HCV, Pilot Study
Official title: Lung Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Lung Transplant Infection
Hepatitis C
Keywords: Lung
Transplant
Hepatitis C
DAAs
Epclusa
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2017-04-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Investigators aim to transplant 20 HCV- recipients with end-stage lung disease from transplant wait-list using lungs from HCV+ donors. Donor lungs will be selected based on usual donor selection criteria evaluating blood gas analysis, chest imaging, bronchoscopy findings, and assessment in the operating room. Once lungs meet criteria for transplantation, they will be retrieved in standard fashion, transported to Toronto General Hospital in cold static preservation, placed on EVLP for 6 hours, and transplanted to consented recipients.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of transplantation from HCV positive donors to HCV negative recipients
timeFrame: 6 months
Secondary outcomes:
measure: Incidence of HCV transmission
timeFrame: 6 months
measure: Correlation between viral loads and recipient infection
timeFrame: 6 months
measure: Time to viremia development
timeFrame: 6 months
measure: HCV cure rates
timeFrame: 6 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Marcelo Cypel, MD MSc FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.