Transplantation Using Hepatitis C Positive Donors, A Safety Trial

Jordan Feld

Status and phase: Enrolling; Phase 3

Conditions: Kidney Pancreas Infection; Lung Transplant Infection; Hepatitis C; Kidney Transplant Infection; Heart Transplant Infection

Treatments: Drug: Ezetimibe 10Mg Oral Tablet; Drug: Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet; Device: Ex Vivo Lung Perfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04017338

JF-8-2018

Details and patient eligibility

About

The success of transplantation is significantly hindered by the lack of sufficient number of available donors. Many potential donor organs 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 organs from HCV-infected donors into HCV-uninfected recipients. Prior to transplantation, recipients will receive an initial dose of highly effective antiviral prophylaxis using approved direct-acting antivirals (DAAs) Glecaprevir/Pibrentasvir (G/P) and they will also receive ezetimibe, a cholesterol-lowering medication that also blocks entry of HCV into liver cells. They will then receive daily dosing of the same medications for 7 days after transplant. The aim of the study is to show that transplantation of organs from HCV+ donors is safe in the era of DAAs. The investigators hypothesize that rates of HCV transmission to recipients will be prevented by the use of DAA prophylaxis 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 organ transplantations.

Full description

The investigators aim to transplant 40 recipients with end-stage organ disease (20 lung, and 20 other organs) using organs from HCV+ donors. Lungs to be used for transplantation will be exposed to ex vivo lung perfusion with use of ultraviolet C light during perfusion if clinically indicated for lung-related outcomes (ie. not determined by the study investigators). Ex vivo organ perfusion will not be used for other organs. Recipients who are scheduled to receive an HCV-infected organ will receive glecaprevir (300mg)/pibrentasvir (120mg) supplied as three fixed-dose combination tablets once a day starting prior to the transplant as soon the patient is in the hospital and it is confirmed that the transplant is proceeding. HCV treatment will continue for 7 days post-transplant (total 8 doses). Recipients will also receive ezetimibe (10 mg) once daily starting at the same time as G/P and continued until 7 days post-transplant. Recipients will have blood samples taken daily for the first 2 weeks and then weekly until 12 weeks post-transplant for HCV PCR (with additional final sample taken at 6 months post-transplant). The investigators hypothesize that HCV transmission to recipients will be prevented by the use of potent DAA prophylaxis plus ezetimibe with or without ex vivo organ perfusion in the immediate peri-operative period.

Enrollment: 40 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Donor Inclusion Criteria:

• Age <70
• NAT+ HCV donor

Donor Exclusion Criteria:

• HIV positive or HTLV 1/2 positive
• Hepatitis B surface Antigen positive
• Any medical issues in the donor that would normally clinically exclude the donor (e.g. history of cancer, evidence of organ dysfunction, etc)
• Age>70

Recipient Inclusion Criteria:

• Recipients listed for kidney, kidney-pancreas, pancreas transplant alone, heart, or lung transplant
• HCV NAT negative
• Provides written informed consent

Recipient Exclusion Criteria:

• Chronic liver disease with > stage 2 fibrosis
• Participating in another interventional clinical trial
• Recipient listed for liver transplant
• Known allergy or contraindication to Glecaprevir/Pibrentasvir or ezetimibe

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Non Randomized Intervention

Experimental group

Description:

Intervention description: recipients on the wait-list for lung, heart, kidney, and/or pancreas transplants will all receive antiviral treatment in the form of 8 total doses of oral tablets. Lung recipients will also receive donor lungs that are treated with normothermic EVLP (details of both described below). Drug: All recipients will receive glecaprevir (300mg)/pibrentasvir (120mg) supplied as three tablets per dose 6-12 hours prior to transplant, and for 7 days post-transplant. Other Names: Maviret. Patients will also receive ezetimibe (10mg), supplied as one tablet per dose to be taken at the same time as Maviret tablets (6-12 hours prior to transplant in addition to 7 daily doses post-transplant). 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 names: Normothermic EVLP.

Treatment:

Drug: Ezetimibe 10Mg Oral Tablet

Device: Ex Vivo Lung Perfusion

Drug: Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet