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

NCT ID: NCT00948194

Last Updated: 2021-05-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2015-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Liver Transplantation Ischemia/Reperfusion Injury Oxidative Injury

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

No nitric oxide

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Nitric Oxide

Will receive Nitric oxide and other standard inhaled anesthetics

Group Type EXPERIMENTAL

Nitric Oxide

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Nitric Oxide

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

INOmax

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Matthew J. Fiegel, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

09-0137

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Delayed Infusion of DCreg in Living Donor Liver Transplantation
NCT04208919 ACTIVE_NOT_RECRUITING PHASE1/PHASE2
Dexmedetomidine and Liver Transplantation
NCT03770130 COMPLETED EARLY_PHASE1