Study to Evaluate if Inhaled Nitric Oxide Improves Liver Function After Transplantation

This study has been completed.
Sponsor:
Collaborators:
INO Therapeutics
University of Washington
Information provided by (Responsible Party):
Rakesh Patel, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00582010
First received: December 20, 2007
Last updated: November 5, 2014
Last verified: October 2014
  Purpose

This blinded, placebo-controlled study will administer inhaled nitric oxide to patients undergoing liver transplantation. The purpose of the study is to test if inhaled nitric oxide prevents liver injury associated with the restoration of blood flow. The premise of the current study is provided by previous studies which document a protective effect of inhaled nitric oxide in this clinical setting.


Condition Intervention Phase
Reperfusion Injury
Liver Injury
Drug: inhaled nitric oxide
Drug: nitrogen gas
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Inhaled Nitric Oxide on Ischemia-Reperfusion Injury in Human Liver During Transplantation

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels) [ Time Frame: baseline and 96 hours after baseline ] [ Designated as safety issue: Yes ]
    The faster the percent decrease of AST reflect the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. The rate was calculated by measuring AST levels at baseline and at 96 hours post baseline. (AST levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of AST relative to baseline).

  • Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels) [ Time Frame: baseline and 96 hours after baseline ] [ Designated as safety issue: Yes ]
    The faster the percent decrease ALT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. . (ALT levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of ALT relative to baseline).

  • Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels) [ Time Frame: baseline and 96 hours after baseline ] [ Designated as safety issue: Yes ]
    The faster the percent increase of alkaline phosphatase reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an increase; a negative percentage reflects a decrease.

  • Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT)) [ Time Frame: baseline and 96 hours after baseline ] [ Designated as safety issue: Yes ]
    The faster the percent increase of PT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase.

  • Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels) [ Time Frame: baseline and 96 hours after baseline ] [ Designated as safety issue: Yes ]
    A positive percent reflects an decrease; a negative percentage reflects a increase.

  • Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications) [ Time Frame: baseline to 9 months after transplantation ] [ Designated as safety issue: No ]
    Number of complications due to hepatobiliary events.

  • Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery [ Time Frame: baseline to 9 months post surgery ] [ Designated as safety issue: No ]
    Number of any complication reported by subjects at 9 months after surgery


Secondary Outcome Measures:
  • Effect of iNO on Hosptial Length of Stay [ Time Frame: from surgery through discharge from hospital ] [ Designated as safety issue: Yes ]
    number of days subject in hospital after surgery until discharge

  • Effect of iNO on SICU Stay [ Time Frame: baseline to discharge for SICU ] [ Designated as safety issue: Yes ]
    Number of minutes after surgery subject remained in SICU


Enrollment: 80
Study Start Date: April 2008
Study Completion Date: October 2012
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. Experimental
iNO administration
Drug: inhaled nitric oxide
inhaled 80ppm for duration of surgery.
Other Name: iNO
Placebo Comparator: 2. Placebo
Placebo (nitrogen)
Drug: nitrogen gas
inhaled

Detailed Description:

Specifically, presenting ischemia-reperfusion injury to transplanted livers remains a therapeutic goal in improving liver function and potentially expanding the number of transplantable livers. This study aims to assess the efficacy of inhaled nitric oxide to limit ischemia-reperfusion injury in transplanted livers and by doing so improve liver function post transplantation and decrease patient hospital length of stays.

  Eligibility

Ages Eligible for Study:   19 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients > 19 yr of age scheduled to undergo liver transplantation.

Exclusion Criteria:

  • Patients < 19 yr of age
  • Patients undergoing re-transplantation or dual organ transplantation
  • Patients with underlying pulmonary complications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00582010

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Washington
University of Washington
Seattle, Washington, United States, 98195-6540
Sponsors and Collaborators
University of Alabama at Birmingham
INO Therapeutics
University of Washington
Investigators
Principal Investigator: Rakesh P Patel, PhD University of Alabama at Birmingham
Principal Investigator: Keith A Jones, MD University of Alabama at Birmingham
Principal Investigator: Devin E Eckhoff, MD University of Alabama at Birmingham
Study Director: John S Bynon, MD University of Alabama at Birmingham
Study Director: Blair Smith, MD University of Alabama at Birmingham
Study Chair: Clark Cross, MD University of Alabama at Birmingham
Study Director: Luc Frenette, MD University of Alabama at Birmingham
Principal Investigator: John D Lang, MD University of Washington
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rakesh Patel, Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00582010     History of Changes
Other Study ID Numbers: F070112003
Study First Received: December 20, 2007
Results First Received: September 30, 2013
Last Updated: November 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Alabama at Birmingham:
ischemia-reperfusion
nitric oxide
inflammation
cell-death
Liver-function post transplantation

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

ClinicalTrials.gov processed this record on July 05, 2015