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
|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|
|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)|
|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|
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
- 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).
- 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).
- 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.
- 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.
- 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).
- 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).
- 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)
- 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.
- 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).
- 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)
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
|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|
|Principal Investigator:||Jordan Feld, MD, MPH||University Health Network Toronto General Hospital|