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

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ClinicalTrials.gov Identifier: NCT00948194
Recruitment Status : Completed
First Posted : July 29, 2009
Last Update Posted : May 9, 2016
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Liver Transplantation Ischemia/Reperfusion Injury Oxidative Injury Drug: Nitric Oxide Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation
Study Start Date : October 2009
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: No nitric oxide
This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics
Experimental: Nitric Oxide
Will receive Nitric oxide and other standard inhaled anesthetics
Drug: Nitric Oxide
Inhalation - 40 ppm, at the initiation of anesthesia to the end of surgery
Other Name: INOmax




Primary Outcome Measures :
  1. To determine if inhaled nitric oxide has beneficial effects on overall outcome after extended criteria donor (EDC) liver transplantation [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. To construct a plasma metabolic/protein profile of I/R injury in transplanted livers [ Time Frame: 3 years ]
  2. To examine the effects of nitric oxide on protein synthesis and metabolism following ECD liver transplantation [ Time Frame: 3 years ]


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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00948194


Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Matthew J. Fiegel, M.D. University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00948194     History of Changes
Other Study ID Numbers: 09-0137
First Posted: July 29, 2009    Key Record Dates
Last Update Posted: May 9, 2016
Last Verified: May 2016

Keywords provided by University of Colorado, Denver:
Extended Donor Criteria

Additional relevant MeSH terms:
Wounds and Injuries
Ischemia
Reperfusion Injury
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents