Clinical trial NCT00718575: The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Liver Transplantation
Keywords: Liver Disease
Transplantation
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2008-07-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Reperfusion injury determined by peak AST
timeFrame: first 24 hours post-operative
Secondary outcomes:
measure: Biliary Complications, infection and rejection
timeFrame: first month post-transplantation
measure: graft and patient survival; length of hospital stay; length of ICU stay
timeFrame: 30 days and 90 days post-transplantation
measure: Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes
timeFrame: immediately pre-removal and post- transplantation
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network (Toronto General Hospital)
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Markus Selzner, M.D.
role: PRINCIPAL_INVESTIGATOR
References: