Lung Transplant InfectionPhase 3NCT04017338
Transplantation Using Hepatitis C Positive Donors, A Safety Trial
A Phase 3 study testing Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet, Ezetimibe 10Mg Oral Tablet and Ex Vivo Lung Perfusion in people with Lung Transplant Infection and Heart Transplant Infection, run by Jordan Feld at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lung Transplant Infection, Heart Transplant Infection, Kidney Transplant Infection
- What is being tested?
- Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet, Ezetimibe 10Mg Oral Tablet and Ex Vivo Lung Perfusion
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 6 Aug 2018to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
University Health Network Toronto General Hospital
Toronto, Ontario, M5G 2N2
Jordan Feld, MD, MPH, 416-340-4800 ext. 4584, Jordan.Feld@uhn.ca
Nellie Kamkar, MSc, 416-340-4800 ext. 6220, Nellie.Kamkar@uhn.ca
About this study
Official title: Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Safety Trial
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.
Read the 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.
- Conditions
- Lung Transplant Infection, Heart Transplant Infection, Kidney Transplant Infection, Kidney Pancreas Infection, Hepatitis C
- Being tested
- Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet, Ezetimibe 10Mg Oral Tablet, Ex Vivo Lung Perfusion
- Keywords
- Organ Transplant, Hepatitis C Virus, Direct-Acting Antivirals (DAAs)
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glecaprevir 300 MG / Pibrentasvir 120 MG Oral TabletDrug
Also called Maviret
A potent and effective antiviral medication that has recently been approved for use in Canada with over 99% cure rates.
Ezetimibe 10Mg Oral TabletDrug
A cholesterol-lowering medication that also blocks entry of HCV into liver cells.
Ex Vivo Lung PerfusionDevice
Also called Normothermic EVLP
A technology that allows for the assessment and treatment of lungs prior to transplant.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet; Drug: Ezetimibe 10Mg Oral Tablet; Device: Ex Vivo Lung Perfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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.
Measured: 30 days
Secondary outcomes (7)
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.
Measured: 1 year
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).
Measured: 1 year
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).
Measured: 1 year
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)
Measured: 1 year
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.
Measured: 1 year
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).
Measured: 1 year
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)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start6 Aug 2018
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung Transplant InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jordan Feld
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto
- Responsible party
- Sponsor-investigator, Jordan Feld, University Health Network, Toronto
- Investigators
- Jordan Feld, MD, MPH, Principal investigator, University Health Network Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017338
- Sponsor's protocol ID
- JF-8-2018
- Status last verified
- Jul 2019
- First submitted
- 2 Jul 2019
- Last updated
- 12 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32389183
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transplantation Using Hepatitis C Positive Donors to Hepatitis C Negative Recipients: A Safety Trial
- ClinicalTrials.gov ID
- NCT04017338
- Acronym / sponsor ID
- JF-8-2018
- 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)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Jordan FeldUniversity, hospital or other
- Collaborators
- University Health Network, Toronto
- Study start
- 6 Aug 2018 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 12 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Non Randomized Intervention | Experimental | Drug: Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet, Drug: Ezetimibe 10Mg Oral Tablet, Device: Ex Vivo Lung PerfusionIntervention 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glecaprevir 300 MG / Pibrentasvir 120 MG Oral TabletAlso: MaviretA potent and effective antiviral medication that has recently been approved for use in Canada with over 99% cure rates. | Drug | Non Randomized Intervention |
| Ezetimibe 10Mg Oral TabletA cholesterol-lowering medication that also blocks entry of HCV into liver cells. | Drug | Non Randomized Intervention |
| Ex Vivo Lung PerfusionAlso: Normothermic EVLPA technology that allows for the assessment and treatment of lungs prior to transplant. | Device | Non Randomized Intervention |
Primary outcome
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.
7 secondary outcomes
Long-Term Organ Function using Spirometry for Lung Recipients
Time frame: 1 year
Long-Term Organ Function using Exercise Tolerance for Lung Recipients
Time frame: 1 year
Long-Term Organ Function for Pancreas Recipients
Time frame: 1 year
Long-Term Organ Function for Kidney Recipients
Time frame: 1 year
Long-Term Organ Function for Heart Recipients
Time frame: 1 year
Acute Cellular Rejection
Time frame: 1 year
HCV Seroconversion
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2019.
- Derived from this study: PubMed 32389183Feld 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordan Feld, MD, MPH principal investigator
University Health Network Toronto General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Glecaprevir 300 MG / Pibrentasvir 120 MG Oral Tablet, Ezetimibe 10Mg Oral Tablet and Ex Vivo Lung Perfusion in people with Lung Transplant Infection and Heart Transplant Infection, run by Jordan Feld at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jordan Feld, MD, MPH (416-340-4800 ext. 4584, Jordan.Feld@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Post-transplant Survival [Safety] (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017338, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2019.