The Effects of Glucose/Ischemic Preconditioning on Reperfusion Injury in Deceased-Donor Liver Transplantation

Liver Transplantation Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00718575
• Other study ID #: 07-0587-AE
• Status: Terminated
• Phase: Phase 3
• First received: July 16, 2008
• Last updated: July 24, 2014
• Start date: August 2008
• Est. completion date: March 2012

Study information

• Verified date: June 2012
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: March 2012
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Transplantation
• Reperfusion Injury

Intervention

Procedure:
• Glucose/Ischemic Preconditioning Pre-treatment
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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reperfusion injury determined by peak AST		first 24 hours post-operative	No
Secondary	Biliary Complications, infection and rejection		first month post-transplantation	Yes
Secondary	graft and patient survival; length of hospital stay; length of ICU stay		30 days and 90 days post-transplantation	Yes
Secondary	Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes		immediately pre-removal and post- transplantation	No