Transplantation Using Hepatitis C Positive Donors, A Safety Trial

NCT ID: NCT04017338

Last Updated: 2019-07-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-06
• Study Completion Date: 2024-12-31

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non Randomized Intervention

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.

Group Type: EXPERIMENTAL

Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet

Intervention Type: DRUG

A potent and effective antiviral medication that has recently been approved for use in Canada with over 99% cure rates.

Ezetimibe 10Mg Oral Tablet

Intervention Type: DRUG

A cholesterol-lowering medication that also blocks entry of HCV into liver cells.

Ex Vivo Lung Perfusion

Intervention Type: DEVICE

A technology that allows for the assessment and treatment of lungs prior to transplant.

Interventions

Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet

A potent and effective antiviral medication that has recently been approved for use in Canada with over 99% cure rates.

Intervention Type: DRUG

Ezetimibe 10Mg Oral Tablet

A cholesterol-lowering medication that also blocks entry of HCV into liver cells.

Intervention Type: DRUG

Ex Vivo Lung Perfusion

A technology that allows for the assessment and treatment of lungs prior to transplant.

Intervention Type: DEVICE

Other Intervention Names

Maviret; Normothermic EVLP

Eligibility Criteria

Inclusion Criteria

• Age <70
• NAT+ HCV donor

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

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

• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Jordan Feld

OTHER

Sponsor Role: lead

Responsible Party

Jordan Feld

Hepatologist and Senior Scientist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jordan Feld, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University Health Network Toronto General Hospital

Locations

University Health Network Toronto General Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Jordan Feld, MD, MPH

Role: CONTACT

Jordan.Feld@uhn.ca

416-340-4800 ext. 4584

Nellie Kamkar, MSc

Role: CONTACT

Nellie.Kamkar@uhn.ca

416-340-4800 ext. 6220

Facility Contacts

Jordan Feld, MD, MPH

Role: primary

Jordan.Feld@uhn.ca

416-340-4800 ext. 4584

Nellie Kamkar, MSc

Role: backup

Nellie.Kamkar@uhn.ca

416-340-4800 ext. 6220

References

Feld JJ, Cypel M, Kumar D, Dahari H, Pinto Ribeiro RV, Marks N, Kamkar N, Bahinskaya I, Onofrio FQ, Zahoor MA, Cerrochi O, Tinckam K, Kim SJ, Schiff J, Reichman TW, McDonald M, Alba C, Waddell TK, Sapisochin G, Selzner M, Keshavjee S, Janssen HLA, Hansen BE, Singer LG, Humar A. Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study. Lancet Gastroenterol Hepatol. 2020 Jul;5(7):649-657. doi: 10.1016/S2468-1253(20)30081-9. Epub 2020 May 6.

Reference Type: DERIVED

PMID: 32389183 (View on PubMed)

Other Identifiers

JF-8-2018

Identifier Type: -

Identifier Source: org_study_id