Liver TransplantationPhase 3NCT00718575
The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation
A Phase 3 study testing Glucose/Ischemic Preconditioning Pre-treatment in people with Liver Transplantation, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Standard liver retrieval procedures for transplantation from a deceased donor inevitably result in a "reperfusion injury" to the liver tissue. The purpose of this research study is to find out whether treatment of the liver with a "preconditioning" protocol before its removal from the donor will help reduce any of… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- Glucose/Ischemic Preconditioning Pre-treatment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2008to Mar 2012
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipient 18 years of age or older
- Recipient with chronic end-stage liver disease
- Deceased donor liver transplant
- Recipient capable of providing written informed consent
- Whole organ graft from donors aged 60 years or older
Who cannot join
- Fulminant liver failure
- Objection by any other member of the retrieval team
- Split-liver grafts
- Donor that has received total parenteral nutrition within 24hr of organ retrieval Donors from whom the pancreas and/or small bowel are also being retrieved
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network (Toronto General Hospital)
Toronto, Ontario, M5G 2N2
About this study
Official title: A Prospective, Randomized Trial to Investigate the Effects of Glucose/ Ischemic Preconditioning Donor Pre-treatment on Reperfusion Injury in Deceased-Donor Liver Transplantation
Standard liver retrieval procedures for transplantation from a deceased donor inevitably result in a "reperfusion injury" to the liver tissue. The purpose of this research study is to find out whether treatment of the liver with a "preconditioning" protocol before its removal from the donor will help reduce any of this injury.
The "preconditioning" treatment being tested has two components. Firstly, a solution of glucose+insulin is infused and secondly, blood flow to the liver is stopped briefly (10 minutes) and then resumed. Both strategies, individually, have been shown to reduce liver tissue injury in human studies.
We hypothesize that combining both strategies will have a clinical benefit to patients and will improve liver function following transplant.
Read the detailed description
Liver transplantation is the only chance of cure for patients with end-stage liver disease. Unfortunately, standard organ preservation results in an ischemic-reperfusion injury (IRI) at the time of graft implantation. Novel strategies have been proposed to decrease reperfusion injury and improve graft function. This study will be the first to combine both strategies in a randomized, prospective trial. The intervention will occur during the retrieval surgery prior to cold preservation. Briefly, a glucose and insulin solution will be infused via the mesenteric vein at a controlled rate. Immediately prior to cross-clamping, blood supply to the liver will be restricted for 10 minutes and then resumed for 10 minutes before beginning cold preservation. All remaining surgical procedures, including the recipient surgery, will be performed by standard techniques. The liver recipient does not directly receive any intervention during this study.
- Conditions
- Liver Transplantation
- Being tested
- Glucose/Ischemic Preconditioning Pre-treatment
- Keywords
- Liver Disease, Transplantation
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucose/Ischemic Preconditioning Pre-treatmentProcedure or surgery
A 20% dextrose+insulin infusion is administered to the liver via the mesenteric vein beginning after cannulation of the mesenteric vein and ending immediately prior to flushing with cold preservation fluid. Also, after completion of the visceral dissection but prior to cross-clamping, ischemic precondition will occur. This involves occluding the portal vein and hepatic artery to stop blood flow for 10 minutes, then restoring blood flow for 10 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Deceased liver donors that are randomized to this arm will receive the Glucose/Ischemic Preconditioning pre-treatment intra-operatively prior to starting cold preservation of the organ Receives: Procedure: Glucose/Ischemic Preconditioning Pre-treatment |
| 2 | No intervention | Neither donors nor recipients receive any intervention. All procedures will be performed according to our institution's standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reperfusion injury determined by peak AST
Measured: first 24 hours post-operative
Secondary outcomes (3)
Biliary Complications, infection and rejection
Measured: first month post-transplantation
graft and patient survival; length of hospital stay; length of ICU stay
Measured: 30 days and 90 days post-transplantation
Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes
Measured: immediately pre-removal and post- transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2008 (estimated)
- Study startAug 2008
- Primary completionJun 2010
- Study completionMar 2012
Why it stopped: too few patients meeting current eligibility criteria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Markus Selzner, M.D., Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00718575
- Sponsor's protocol ID
- 07-0587-AE
- Status last verified
- Jun 2012
- First submitted
- 16 Jul 2008
- Last updated
- 25 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized Trial to Investigate the Effects of Glucose/ Ischemic Preconditioning Donor Pre-treatment on Reperfusion Injury in Deceased-Donor Liver Transplantation
- ClinicalTrials.gov ID
- NCT00718575
- Acronym / sponsor ID
- 07-0587-AE
- Conditions
- Liver Transplantation
- Keywords
- Liver Disease, Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: too few patients meeting current eligibility criteria
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 18 Jul 2008 (estimated)
- 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.
Standard liver retrieval procedures for transplantation from a deceased donor inevitably result in a "reperfusion injury" to the liver tissue. The purpose of this research study is to find out whether treatment of the liver with a "preconditioning" protocol before its removal from the donor will help reduce any of this injury.
The "preconditioning" treatment being tested has two components. Firstly, a solution of glucose+insulin is infused and secondly, blood flow to the liver is stopped briefly (10 minutes) and then resumed. Both strategies, individually, have been shown to reduce liver tissue injury in human studies.
We hypothesize that combining both strategies will have a clinical benefit to patients and will improve liver function following transplant.
Detailed description
Liver transplantation is the only chance of cure for patients with end-stage liver disease. Unfortunately, standard organ preservation results in an ischemic-reperfusion injury (IRI) at the time of graft implantation. Novel strategies have been proposed to decrease reperfusion injury and improve graft function. This study will be the first to combine both strategies in a randomized, prospective trial. The intervention will occur during the retrieval surgery prior to cold preservation. Briefly, a glucose and insulin solution will be infused via the mesenteric vein at a controlled rate. Immediately prior to cross-clamping, blood supply to the liver will be restricted for 10 minutes and then resumed for 10 minutes before beginning cold preservation. All remaining surgical procedures, including the recipient surgery, will be performed by standard techniques. The liver recipient does not directly receive any intervention during this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Glucose/Ischemic Preconditioning Pre-treatmentDeceased liver donors that are randomized to this arm will receive the Glucose/Ischemic Preconditioning pre-treatment intra-operatively prior to starting cold preservation of the organ |
| 2 | No intervention | –Neither donors nor recipients receive any intervention. All procedures will be performed according to our institution's standard of care. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Recipient 18 years of age or older
- Recipient with chronic end-stage liver disease
- Deceased donor liver transplant
- Recipient capable of providing written informed consent
- Whole organ graft from donors aged 60 years or older
Key exclusion criteria (4 listed)
- Fulminant liver failure
- Objection by any other member of the retrieval team
- Split-liver grafts
- Donor that has received total parenteral nutrition within 24hr of organ retrieval Donors from whom the pancreas and/or small bowel are also being retrieved
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 |
|---|---|---|
| Glucose/Ischemic Preconditioning Pre-treatmentA 20% dextrose+insulin infusion is administered to the liver via the mesenteric vein beginning after cannulation of the mesenteric vein and ending immediately prior to flushing with cold preservation fluid. Also, after completion of the visceral dissection but prior to cross-clamping, ischemic precondition will occur. This involves occluding the portal vein and hepatic artery to stop blood flow for 10 minutes, then restoring blood flow for 10 minutes. | Procedure or surgery | 1 |
Primary outcome
Reperfusion injury determined by peak AST
Time frame: first 24 hours post-operative
3 secondary outcomes
Biliary Complications, infection and rejection
Time frame: first month post-transplantation
graft and patient survival; length of hospital stay; length of ICU stay
Time frame: 30 days and 90 days post-transplantation
Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes
Time frame: immediately pre-removal and post- transplantation
Results and safety
The study was stopped early (reason given: too few patients meeting current eligibility criteria). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2014.
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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.
Markus Selzner, M.D. principal investigator
University Health Network, Toronto
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 Glucose/Ischemic Preconditioning Pre-treatment in people with Liver Transplantation, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jul 2014. 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?
The study was stopped early (reason given: too few patients meeting current eligibility criteria). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reperfusion injury determined by peak AST (time frame: first 24 hours post-operative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jul 2014.