Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation

NCT00948194 | Terminated Results

• 1 other identifier: 09-0137
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria(EDC)liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft. In reviewing the literature, no uniform extended criteria donor classification exists. The characteristics most associated with liver graft failure appear to be cold ischemia time greater than 10 hours, warm ischemia time greater than 40 minutes, donor age \> 55 years of age, donor hospitalization \> 5 days, a donation after cardiac death (DCD) graft, and a split graft. The researchers will exclude warm ischemia time as this is impossible to predict prior to the transplantation. Any donor meeting at least one of the other criteria will be classified as an EDC donor. Hypothesis 1: Inhaled nitric oxide will improve overall outcome of liver recipients after EDC liver transplantation

• Suppression of oxidative injury will improve graft function postoperatively as measured by International Normalized Ratio (INR) bilirubin, transaminases, and duration of hospital stay. Hypothesis 2: The mechanisms of therapeutic efficacy of inhaled nitric oxide is based on reduction in post-reperfusion oxidative injury as readily measured by the detectable changes in the protein and metabolic profiles in plasma of patients treated with inhaled-NO
• Nuclear Magnetic Resonance (NMR)-based metabolic markers (xanthine end-products, lactate, and hepatic osmolytes) that are consistent with acute liver injury will be decreased in NO-treated recipients.
• Protein markers of reperfusion injury (argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1) will be greater in the plasma of patients who are not treated with inhaled-NO
• Reduced oxidative injury will be reflected by a decrease in the number of mitochondrial peroxiredoxins isoforms and the number that are oxidized in NO-treated liver recipients.

Conditions

Liver Transplantation; Ischemia/Reperfusion Injury; Oxidative Injury

Keywords

Extended Donor Criteria

Outcome Measures

Primary Outcomes (1)

• To Determine if Inhaled Nitric Oxide Has Beneficial Effects on Overall Outcome After Extended Criteria Donor (EDC) Liver Transplantation

  3 years

Secondary Outcomes (2)

• To Construct a Plasma Metabolic/Protein Profile of I/R Injury in Transplanted Livers

  3 years

• To Examine the Effects of Nitric Oxide on Protein Synthesis and Metabolism Following Extended Criteria Donor Liver Transplantation

  3 years

Study Arms (2)

No nitric oxide

NO INTERVENTION

This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics

Nitric Oxide

EXPERIMENTAL

Will receive Nitric oxide and other standard inhaled anesthetics

Drug: Nitric Oxide

Interventions

Nitric Oxide DRUG

Inhalation - 40 ppm, at the initiation of anesthesia to the end of surgery

Also known as: INOmax

Nitric Oxide

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 - 69 years of age
• moderate to severe liver disease (MELD score 22 to 30)
• is receiving a extended donor criteria liver graft

You may not qualify if:

• undergoing multi-organ transplant
• years or older
• diagnosed with hepatocarcinoma
• diagnosed with either hepatopulmonary syndrome or pulmonary hypertension
• pregnant

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Nitric Oxide; Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals; Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Nick Naughton
• Organization: University of Colorado Denver

nick.naughton@cuanschutz.edu

303-724-0833

Study Officials

• Matthew J. Fiegel, M.D.

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2009
• First Posted: July 29, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 28, 2021
• Results First Posted: May 28, 2021

Record last verified: 2021-05

Locations

US (1)