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

NCT00582010 | Completed Phase 2 Results

• 1 other identifier: F070112003
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Reperfusion Injury; Liver Injury

Keywords

ischemia-reperfusion; nitric oxide; inflammation; cell-death; Liver-function post transplantation

Outcome Measures

Primary Outcomes (7)

• Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels)

  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).

  baseline and 96 hours after baseline

• Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels)

  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).

  baseline and 96 hours after baseline

• Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels)

  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.

  baseline and 96 hours after baseline

• Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT))

  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.

  baseline and 96 hours after baseline

• Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels)

  A positive percent reflects an decrease; a negative percentage reflects a increase.

  baseline and 96 hours after baseline

• Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications)

  Number of complications due to hepatobiliary events.

  baseline to 9 months after transplantation

• Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery

  Number of any complication reported by subjects at 9 months after surgery

  baseline to 9 months post surgery

Secondary Outcomes (2)

• Effect of iNO on Hosptial Length of Stay

  from surgery through discharge from hospital

• Effect of iNO on SICU Stay

  baseline to discharge for SICU

Study Arms (2)

1. Experimental

EXPERIMENTAL

iNO administration

Drug: inhaled nitric oxide

2. Placebo

PLACEBO COMPARATOR

Placebo (nitrogen)

Drug: nitrogen gas

Interventions

inhaled nitric oxide DRUG

inhaled 80ppm for duration of surgery.

Also known as: iNO

1. Experimental

nitrogen gas DRUG

inhaled

2. Placebo

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients \< 19 yr of age
• Patients undergoing re-transplantation or dual organ transplantation
• Patients with underlying pulmonary complications

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Mallinckrodt: collaborator
• University of Washington: collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Washington

Seattle, Washington, 98195-6540, United States

Location

Related Publications (2)

• Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest. 2007 Sep;117(9):2583-91. doi: 10.1172/JCI31892.

  PMID: 17717604 BACKGROUND

• Lang JD Jr, Smith AB, Brandon A, Bradley KM, Liu Y, Li W, Crowe DR, Jhala NC, Cross RC, Frenette L, Martay K, Vater YL, Vitin AA, Dembo GA, Dubay DA, Bynon JS, Szychowski JM, Reyes JD, Halldorson JB, Rayhill SC, Dick AA, Bakthavatsalam R, Brandenberger J, Broeckel-Elrod JA, Sissons-Ross L, Jordan T, Chen LY, Siriussawakul A, Eckhoff DE, Patel RP. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One. 2014 Feb 12;9(2):e86053. doi: 10.1371/journal.pone.0086053. eCollection 2014.

  PMID: 24533048 DERIVED

MeSH Terms

Conditions

Reperfusion Injury; Inflammation

Interventions

Nitrogen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Elements; Inorganic Chemicals; Gases

Results Point of Contact

• Title: Rakesh Patel
• Organization: University of Alabama at Birmingham

rakeshp@uab.edu

205-934-3411

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• John S Bynon, MD

  University of Alabama at Birmingham

  STUDY DIRECTOR

• Blair Smith, MD

  University of Alabama at Birmingham

  STUDY DIRECTOR

• Clark Cross, MD

  University of Alabama at Birmingham

  STUDY CHAIR

• Luc Frenette, MD

  University of Alabama at Birmingham

  STUDY DIRECTOR

• John D Lang, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 28, 2007
• Study Start: April 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: October 1, 2012
• Last Updated: November 6, 2014
• Results First Posted: November 6, 2014

Record last verified: 2014-10

Locations

US (2)