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

Not Applicable

Terminated

• Conditions: Liver Transplantation; Ischemia/Reperfusion Injury; Oxidative Injury
• Interventions: Drug: Nitric Oxide

• Registration Number: NCT00948194
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-07-24
• Study First Submitted QC: 2009-07-28
• Study First Posted: 2009-07-29
• Study Start: 2009-10
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Results First Submitted: 2021-01-22
• Status Verified: 2021-05
• Results First Submitted QC: 2021-05-26
• Last Update Submitted: 2021-05-26
• Results First Posted: 2021-05-28
• Last Update Posted: 2021-05-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitric Oxide	Nitric Oxide	Will receive Nitric oxide and other standard inhaled anesthetics

Primary Outcome Measures

Name	Time	Method
To Determine if Inhaled Nitric Oxide Has Beneficial Effects on Overall Outcome After Extended Criteria Donor (EDC) Liver Transplantation	3 years

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States