NCT04017338

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Aug 2018

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 6, 2018

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

July 2, 2019

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 12, 2019

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

July 12, 2019

Status Verified

July 1, 2019

Enrollment Period

2.4 years

First QC Date

July 2, 2019

Last Update Submit

July 11, 2019

Conditions

Lung Transplant InfectionHeart Transplant InfectionKidney Transplant InfectionKidney Pancreas InfectionHepatitis C

Keywords

Organ TransplantHepatitis C VirusDirect-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

  • +2 more secondary outcomes

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 TabletDrug: Ezetimibe 10Mg Oral TabletDevice: Ex Vivo Lung Perfusion

Interventions

Glecaprevir 300 MG / Pibrentasvir 120 MG Oral TabletDRUG

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 TabletDRUG

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

Non Randomized Intervention
Ex Vivo Lung PerfusionDEVICE

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

Also known as: Normothermic EVLP
Non Randomized Intervention

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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: 32389183DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

glecaprevirpibrentasvirTabletsEzetimibe

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage FormsPharmaceutical PreparationsAzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Jordan Feld, MD, MPH

    University Health Network Toronto General Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordan Feld, MD, MPH

CONTACT

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

Nellie Kamkar, MSc

CONTACT

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

Study Design

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

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)