Transplanting Hepatitis C Lungs Into Negative Lung Recipients

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

18-67 years of age
Obtained agreement for participation from the lung transplant team
No evident contraindication to lung transplantation other than the underlying lung disorder
Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
No active illicit substance abuse
Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HCV transmission
Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-lung transplantation
Able to provide informed consent

Exclusion Criteria

Hepatocellular carcinoma
HIV positive
HCV RNA positive
Hepatitis B surface antigen and/or DNA positive
Any chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD)) that is occurring in the setting of persistently elevated liver enzymes (patients with Alpha-1-antitrypsin lung disease without hepatic involvement are eligible)
Significant fibrosis (≥F2 on the Fibroscan)-for patients with cystic fibrosis, the cutoff will be 11kPa (cutoff for F2 for patients with chronic cholestatic liver disease), whereas for all other patients the cutoff will be 8kPa (the cutoff for fatty liver disease used in the THINKER study).
Pregnant or nursing (lactating) women
Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and Zepatier/Epclusa
Pre-transplant treatment with amiodarone given the drug-drug interaction between amiodarone and Epclusa
Waitlisted for a multi-organ transplant
Patients with underlying liver disease with or without liver cirrhosis
Patients with cystic fibrosis who have underlying liver disease
Re-transplant candidate
Use of ECMO or mechanical ventilation as a bridge to lung transplantation
Inability to provide study consent
Chronic kidney disease with GFR<50 ml/min/1.73 m^2

Relative contraindications for study subjects that will be reviewed on a case-by-case basis by the Lung Transplant Selection Committee and the Principal Investigators:

Evidence of end organ damage due to diabetes (e.g. retinopathy, nephropathy, ulcerations) and /or brittle diabetes mellitus (e.g. history of diabetic ketoacidosis) and/or uncontrolled diabetes as evidence by a HgbA1C of 7.5-8.5.
Hematologic: Significant coagulation abnormalities, and/or bleeding diatheses.
Active or recent solid or liquid malignancy in the past 5 years (apart from select skin malignancies).
Patient refusal to receive blood products or transfusions during lung transplant surgery.
Psychosocial: Profound neurocognitive impairment with absence of social support.
Active mental illness or psychosocial instability
Inadequate insurance and/or financial support for post-transplant care.
Evidence of drug, tobacco or alcohol abuse within the past six months and failure to satisfy recommended therapy/services/parameters as indicated by social work staff and/or consult team.
History of chronic non-adherence to medical recommendations and/or medications
PRA >10%.
Severe malnutrition, BMI <18
Major chronic disabling comorbidity (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual).
Symptomatic or severe vascular disease (History of CABG, Aorta-femoral surgery)

Donor Organ Selection Criteria

Broad goal: To include donors with confirmed HCV expected to have acceptable post-transplant graft outcomes based on large retrospective lung transplant studies.

Inclusion criteria for donors:

Detectable HCV RNA
Age ≤55 years
PaO2/FiO2 ≥300 on FiO2 = 100% and PEEP=5
Cigarette use history ≤20 pack years
No evidence of cirrhosis
No prior treatment of HCV with a DAA-based therapy
Can be isolated hepatitis B Core IgG positive, but cannot have a detectable HBV Core IgM, HBSAg, and/or HBV DNA (positive HBV NAT test)

Donor Exclusion Criteria:

Donation after circulatory death determination (DCDD)
HIV positive

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Direct-acting antiviral treatment for HCV	Zepatier	-
Direct-acting antiviral treatment for HCV	Epclusa	-

Primary Outcome Measures

Name	Time	Method
Subject Sustained Virologic Response (SVR-12) at 12-weeks Post-treatment	Baseline to 12 weeks	The primary outcome measure is Sustained Virologic Response (SVR) rate at 12 weeks (number of subjects with SVR; negative HCV RNA after completing therapy) / (number of subjects treated post-lung transplantation). SVR will be based on the standard definition of SVR-12, defined as an undetectable HCV RNA in a subject's serum 12 weeks after completing treatment for HCV (12 weeks after the subject takes the last dose of Zepatier, Epclusa, or another appropriate antiviral treatment).
Major Adverse Events Attributable to HCV Therapy in Post-lung Transplant Patients Post-lung Transplant Patients	Baseline to 52 weeks

Secondary Outcome Measures

Name	Time	Method

Transplanting Hepatitis C Lungs Into Negative Lung Recipients

Recruitment & Eligibility

Study & Design

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