Liver Injury, Reperfusion Injury
Conditions
Keywords
ischemia-reperfusion, nitric oxide, inflammation, cell-death, Liver-function post transplantation
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.
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.
Interventions
DRUGinhaled nitric oxide
inhaled 80ppm for duration of surgery.
DRUGnitrogen gas
inhaled
Sponsors
Mallinckrodt
University of Washington
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery | baseline to 9 months post surgery | Number of any complication reported by subjects at 9 months after surgery |
| Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels) | baseline and 96 hours after baseline | 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) | baseline to 9 months after transplantation | Number of complications due to hepatobiliary events. |
| Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels) | baseline and 96 hours after baseline | 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) | baseline and 96 hours after baseline | 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) | baseline and 96 hours after baseline | 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)) | baseline and 96 hours after baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of iNO on SICU Stay | baseline to discharge for SICU | Number of minutes after surgery subject remained in SICU |
| Effect of iNO on Hosptial Length of Stay | from surgery through discharge from hospital | number of days subject in hospital after surgery until discharge |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Nitric Oxide 80 ppm was administered by inhalation for the duration of surgery | 40 |
| Placebo (Nitrogen Gas) 80 ppm was administered by inhalation for the duration of surgery | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | Inhaled Nitric Oxide | Placebo (Nitrogen Gas) | Total |
|---|---|---|---|
| Age, Continuous | 59 years FULL_RANGE 4 | 61 years | 60 years |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 31 Participants | 33 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 0 / 39 |
| serious Total, serious adverse events | 0 / 40 | 1 / 39 |
Outcome results
Primary
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).
Time frame: baseline and 96 hours after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels) | 62.3 percentage change from baseline | Standard Deviation 26.8 |
| Placebo | Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels) | 62.4 percentage change from baseline | Standard Deviation 34.9 |
Primary
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).
Time frame: baseline and 96 hours after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels) | 83 percentage change from baseline | Standard Deviation 14.6 |
| Placebo | Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels) | 86.4 percentage change from baseline | Standard Deviation 18 |
Primary
Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications)
Number of complications due to hepatobiliary events.
Time frame: baseline to 9 months after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Nitric Oxide | Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications) | 2 Complications |
| Placebo | Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications) | 5 Complications |
Primary
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.
Time frame: baseline and 96 hours after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels) | 239.7 percentage change from baseline | Standard Deviation 672.4 |
| Placebo | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels) | 55 percentage change from baseline | Standard Deviation 96.3 |
Primary
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.
Time frame: baseline and 96 hours after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels) | 6.6 percent change from baseline | Standard Deviation 57 |
| Placebo | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels) | 0.4 percent change from baseline | Standard Deviation 56.7 |
Primary
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.
Time frame: baseline and 96 hours after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inhaled Nitric Oxide | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT)) | 48.9 percentage change from baseline | Standard Deviation 9.9 |
| Placebo | Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT)) | 25.5 percentage change from baseline | Standard Deviation 37.4 |
Primary
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
Time frame: baseline to 9 months post surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Nitric Oxide | Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery | 44 complications |
| Placebo | Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery | 83 complications |
Secondary
Effect of iNO on Hosptial Length of Stay
number of days subject in hospital after surgery until discharge
Time frame: from surgery through discharge from hospital
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Inhaled Nitric Oxide | Effect of iNO on Hosptial Length of Stay | 9.0 days |
| Placebo | Effect of iNO on Hosptial Length of Stay | 9.0 days |
Secondary
Effect of iNO on SICU Stay
Number of minutes after surgery subject remained in SICU
Time frame: baseline to discharge for SICU
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Inhaled Nitric Oxide | Effect of iNO on SICU Stay | 2533 minutes |
| Placebo | Effect of iNO on SICU Stay | 2518 minutes |