Transplantation Using Hepatitis C Positive Donors, A Safety Trial

NCT04017338 | Unknown Phase 3

• 1 other identifier: JF-8-2018
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Organ Transplant; Hepatitis C Virus; Direct-Acting Antivirals (DAAs)

Outcome Measures

Primary Outcomes (3)

• Post-transplant Survival [Safety]

  Survival at 6 months post-transplantation in patients receiving organs from HCV-positive donors reported as a binary variable (survival: yes vs. no).

  6 months

• Incidence of HCV transmission [Safety]

  Incidence of HCV transmission following organ transplantation using HCV-positive donors. The proportion who are HCV RNA positive by PCR at 6 months post-transplantation will be reported as a binary variable (transmission: yes vs. no).

  6 months

• Incidence of treatment-emergent adverse events [Safety and Tolerability]

  The number and type of adverse events that are related to treatment with glecaprevir/pibrentasvir or ezetimibe in the opinion of the investigator will be reported at 30 days.

  30 days

Secondary Outcomes (7)

• Long-Term Organ Function using Spirometry for Lung Recipients

  1 year

• Long-Term Organ Function using Exercise Tolerance for Lung Recipients

  1 year

• Long-Term Organ Function for Pancreas Recipients

  1 year

• Long-Term Organ Function for Kidney Recipients

  1 year

• Long-Term Organ Function for Heart Recipients

  1 year

Study Arms (1)

Non Randomized Intervention

EXPERIMENTAL

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.

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

Interventions

Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet DRUG

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

Also known as: Maviret

Non Randomized Intervention

Ezetimibe 10Mg Oral Tablet DRUG

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

Non Randomized Intervention

Ex Vivo Lung Perfusion DEVICE

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

Also known as: Normothermic EVLP

Non Randomized Intervention

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \<70
• NAT+ HCV donor

You may not qualify if:

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

Sponsors & Collaborators

• Jordan Feld: lead
• University Health Network, Toronto: collaborator

Study Sites (1)

University Health Network Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 32389183 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

glecaprevir; pibrentasvir; Tablets; Ezetimibe

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jordan Feld, MD, MPH

  University Health Network Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordan Feld, MD, MPH

CONTACT

416-340-4800; Jordan.Feld@uhn.ca

Nellie Kamkar, MSc

CONTACT

416-340-4800; Nellie.Kamkar@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Hepatologist and Senior Scientist

Model Details: Investigators aim to transplant 40 recipients (20 lung; 20 other organs) on the transplant wait-list. Donor organs will be selected based on usual donor selection criteria. Recipients will be selected based on usual hospital protocol for selecting suitable recipients. After transplantation, recipients will receive highly effective antiviral prophylaxis using approved direct-acting antivirals (DAAs) Glecaprevir/Pibrentasvir (G/P) and they will also receive ezetimibe, a cholesterol-lowering medication. Additionally, lung transplant recipients will receive donor lungs treated with normothermic ex vivo lung perfusion (EVLP) prior to transplant.

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 12, 2019
• Study Start: August 6, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2024
• Last Updated: July 12, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)