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Lung Transplant HCV, Pilot Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03112044
Recruitment Status : Active, not recruiting
First Posted : April 13, 2017
Last Update Posted : April 22, 2020
Gilead Sciences
Information provided by (Responsible Party):
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 enrolled 20 patients from the Lung transplant wait list in this study. Patients will be followed for 6 months. This will be a single center pilot study.

Condition or disease Intervention/treatment Phase
Lung Transplant Infection Hepatitis C Drug: Sofosbuvir-velpatasvir (400 mg/100 mg) Device: Ex Vivo Lung Perfusion (EVLP) Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lung Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Pilot Study
Actual Study Start Date : September 19, 2017
Actual Primary Completion Date : January 2, 2020
Estimated Study Completion Date : April 17, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
Experimental: 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.
Drug: 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.
Other Name: Epclusa

Device: 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.
Other Name: Normothermic EVLP

Primary Outcome Measures :
  1. Safety of transplantation from HCV positive donors to HCV negative recipients [ Time Frame: 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 :
  1. Incidence of HCV transmission [ Time Frame: 6 months ]
    Incidence of donor to recipient HCV transmission.

  2. Correlation between viral loads and recipient infection [ Time Frame: 6 months ]
    Correlation between donor viremia, EVLP perfusate virus load (PCR), lung tissue virus load at the end of EVLP (PCR) and recipient infection

  3. Time to viremia development [ Time Frame: 6 months ]
    Interval of time from transplantation to development of viremia

  4. HCV cure rates [ Time Frame: 6 months ]
    HCV cure rates after treatment of infected patients

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03112044

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Canada, Ontario
University Health Network Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Sponsors and Collaborators
University Health Network, Toronto
Gilead Sciences
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Principal Investigator: Marcelo Cypel, MD MSc FRCSC University Health Network, Toronto
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University Health Network, Toronto Identifier: NCT03112044    
Other Study ID Numbers: UHNTID006
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
Hepatitis C
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents