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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effects of Inhaled Nitric Oxide on Ischemia-Reperfusion Injury in Human Liver During Transplantation

Conditions
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Reperfusion Injury, Liver Injury

Intervention / Treatment
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* Drug: inhaled nitric oxide
* Drug: nitrogen gas


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Experimental<br>iNO administration | Drug: inhaled nitric oxide<br>* inhaled 80ppm for duration of surgery.<br>* Other names: iNO;|
| Placebo Comparator: 2. Placebo<br>Placebo (nitrogen) | Drug: nitrogen gas<br>* inhaled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of iNO on Hosptial Length of Stay | number of days subject in hospital after surgery until discharge | from surgery through discharge from hospital | 
| Effect of iNO on SICU Stay | Number of minutes after surgery subject remained in SICU | baseline to discharge for SICU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemia-reperfusion, nitric oxide, inflammation, cell-death, Liver-function post transplantation