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Trial record 13 of 20 for:    evlp

Transplantation Using Hepatitis C Positive Donors, A Safety Trial

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ClinicalTrials.gov Identifier: NCT04017338
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
Jordan Feld, University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Lung Transplant Infection Heart Transplant Infection Kidney Transplant Infection Kidney Pancreas Infection Hepatitis C Drug: Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet Drug: Ezetimibe 10Mg Oral Tablet Device: Ex Vivo Lung Perfusion Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Safety Trial
Actual Study Start Date : August 6, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Drug: 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.
Other Name: Maviret

Drug: Ezetimibe 10Mg Oral Tablet
A cholesterol-lowering medication that also blocks entry of HCV into liver cells.

Device: Ex Vivo Lung Perfusion
A technology that allows for the assessment and treatment of lungs prior to transplant.
Other Name: Normothermic EVLP




Primary Outcome Measures :
  1. Post-transplant Survival [Safety] [ Time Frame: 6 months ]
    Survival at 6 months post-transplantation in patients receiving organs from HCV-positive donors reported as a binary variable (survival: yes vs. no).

  2. Incidence of HCV transmission [Safety] [ Time Frame: 6 months ]
    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).

  3. Incidence of treatment-emergent adverse events [Safety and Tolerability] [ Time Frame: 30 days ]
    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.


Secondary Outcome Measures :
  1. Long-Term Organ Function using Spirometry for Lung Recipients [ Time Frame: 1 year ]
    Spirometry (also known as a pulmonary function test) will be used to assess lung function, measured as the Forced Vital Capacity (FVC) in liters.

  2. Long-Term Organ Function using Exercise Tolerance for Lung Recipients [ Time Frame: 1 year ]
    A 6-minute walk test will also be used to assess lung function, measured as the total distance the patient can walk during the span of 6 minutes in meters).

  3. Long-Term Organ Function for Pancreas Recipients [ Time Frame: 1 year ]
    Insulin dependency will be used to assess pancreas function in patients with diabetes, measured as the status of insulin freedom (not needing insulin) after the first year post transplantation. The outcome will be reported as a binary variable (insulin freedom: yes vs. no).

  4. Long-Term Organ Function for Kidney Recipients [ Time Frame: 1 year ]
    Creatinine levels will be used to assess kidney function and will be collected with a blood test. The estimated glomerular filtration rate (eGFR) will then be calculated in milliliters per minute using serum creatinine (Scr). The formula used to calculate eGFR will be using the Modification of Diet in Renal Disease (MDRD) equation, GFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American)

  5. Long-Term Organ Function for Heart Recipients [ Time Frame: 1 year ]
    Left ventricular ejection fraction (the amount of blood leaving the heart during each contraction) will be measured by echocardiography and will be expressed as a percentage.

  6. Acute Cellular Rejection [ Time Frame: 1 year ]
    The incidence of acute cellular rejection following transplantation will be measured as the proportion of patients with biopsy-proven acute cellular rejection of the transplanted organ and will be reported as a binary variable (yes vs. no).

  7. HCV Seroconversion [ Time Frame: 1 year ]
    HCV seroconversion will be measured as the proportion of patients who test positive for antibodies to HCV at 1 year post-transplant and will be reported as a binary variable (HCV antibody positive: yes vs. no)



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04017338


Contacts
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Contact: Jordan Feld, MD, MPH 416-340-4800 ext 4584 Jordan.Feld@uhn.ca
Contact: Nellie Kamkar, MSc 416-340-4800 ext 6220 Nellie.Kamkar@uhn.ca

Locations
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Canada, Ontario
University Health Network Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Jordan Feld, MD, MPH    416-340-4800 ext 4584    Jordan.Feld@uhn.ca   
Contact: Nellie Kamkar, MSc    416-340-4800 ext 6220    Nellie.Kamkar@uhn.ca   
Sponsors and Collaborators
Jordan Feld
University Health Network, Toronto
Investigators
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Principal Investigator: Jordan Feld, MD, MPH University Health Network Toronto General Hospital

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Responsible Party: Jordan Feld, Hepatologist and Senior Scientist, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04017338     History of Changes
Other Study ID Numbers: JF-8-2018
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jordan Feld, University Health Network, Toronto:
Organ Transplant
Hepatitis C Virus
Direct-Acting Antivirals (DAAs)
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Ezetimibe
Anti-Infective Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents