Transplantation Using Hepatitis C Positive Donors, A Safety Trial

Hepatitis C Clinical Trial

Official title:

Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Safety Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04017338
• Other study ID #: JF-8-2018
• Status: Recruiting
• Phase: Phase 3
• Start date: August 6, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2019
• Source: University Health Network, Toronto
• Contact: Jordan Feld, MD, MPH
• Phone: 416-340-4800
• Email: Jordan.Feld[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Heart Transplant Infection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Infection
• Kidney Pancreas Infection
• Kidney Transplant Infection
• Lung Transplant Infection

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	University Health Network Toronto General Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Jordan Feld	University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Long-Term Organ Function using Spirometry for Lung Recipients	Spirometry (also known as a pulmonary function test) will be used to assess lung function, measured as the Forced Vital Capacity (FVC) in liters.	1 year
Secondary	Long-Term Organ Function using Exercise Tolerance for Lung Recipients	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).	1 year
Secondary	Long-Term Organ Function for Pancreas Recipients	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).	1 year
Secondary	Long-Term Organ Function for Kidney Recipients	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)	1 year
Secondary	Long-Term Organ Function for Heart Recipients	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.	1 year
Secondary	Acute Cellular Rejection	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).	1 year
Secondary	HCV Seroconversion	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)	1 year