Hepatitis C, Lung Transplant Infection
Conditions
Keywords
Lung, Transplant, Hepatitis C, DAAs, Epclusa
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.
Interventions
DRUGSofosbuvir-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.
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.
Sponsors
University Health Network, Toronto
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of HCV transmission | 6 months | Incidence of donor to recipient HCV transmission. |
| 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 |
| 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 |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORMarcelo Cypel, MD MSc FRCSC
University Health Network, Toronto
Outcome results
None listed