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

NCT00718575 | Terminated Phase 3

• 1 other identifier: 07-0587-AE
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplantation

Keywords

Liver Disease; Transplantation

Outcome Measures

Primary Outcomes (1)

• Reperfusion injury determined by peak AST

  first 24 hours post-operative

Secondary Outcomes (3)

• Biliary Complications, infection and rejection

  first month post-transplantation

• graft and patient survival; length of hospital stay; length of ICU stay

  30 days and 90 days post-transplantation

• Liver ATP and glycogen content; blood cytokine levels; liver gene expression of pro- and anti-apoptotic genes

  immediately pre-removal and post- transplantation

Study Arms (2)

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

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.

Interventions

Glucose/Ischemic Preconditioning Pre-treatment PROCEDURE

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.

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network (Toronto General Hospital)

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

Glucose

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Markus Selzner, M.D.

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 18, 2008
• Study Start: August 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: March 1, 2012
• Last Updated: July 25, 2014

Record last verified: 2012-06

Locations

CA (1)