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Inhaled NO as an Anti-inflammatory and Anti-reperfusion Agent in Infants and Children Undergoing Cardiopulmonary Bypass

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ClinicalTrials.gov Identifier: NCT00585013
Recruitment Status : Completed
First Posted : January 2, 2008
Results First Posted : November 4, 2015
Last Update Posted : November 4, 2015
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Congenital Heart Disease
Intervention Drug: Nitric Oxide
Enrollment 17
Recruitment Details Patients were randomized by the research perfusionist using sequentially ordered randomization codes. The randomization codes were generated using a computerized random number generator. The entire care team was blinded to the delivery device and drug delivery. Only the study perfusionist was aware of randomization and delivery.
Pre-assignment Details Seventeen patients consented and were enrolled in the study. There were eight consent failures. One patient was disqualified after consent and randomization due to intraoperative findings of a lesion inconsistent with preoperative diagnosis and change in operative plan.
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Period Title: Overall Study
Started 8 8
Completed 8 8
Not Completed 0 0
Arm/Group Title 1 Treatment 2 Placebo Total
Hide Arm/Group Description

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose. Total of all reporting groups
Overall Number of Baseline Participants 8 8 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
<=18 years
8
 100.0%
8
 100.0%
16
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 16 participants
.4  (.1) .4  (.1) .4  (.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 16 participants
Female
1
  12.5%
4
  50.0%
5
  31.3%
Male
7
  87.5%
4
  50.0%
11
  68.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants 8 participants 16 participants
8 8 16
1.Primary Outcome
Title Serum Inflammatory Mediators Post CPB
Hide Description Inflammation measured through the measurement inflammatory mediators, serum interleukin-6, serum interleukin-8, and tumor necrosis factor. Baseline (preoperative, 0h, 12h, 24h, and 48h.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Nitric Oxide Delivery Group Placebo
Hide Arm/Group Description:

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide: Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
Interleukin-6 Preoperative 3.8  (3.5) 3.4  (2.5)
Interleukin-6, 0 hrs 90.9  (44.6) 78.3  (45.7)
Interleukin-6, 12 hrs 51.5  (38.7) 73.3  (67.0)
Interleukin-6, 24 hrs 64.2  (28.4) 80.7  (82.1)
Interleukin-6, 48 hrs 31.2  (30.6) 39.4  (48.9)
Interleukin-8, Preoperative 60.9  (28.8) 39.8  (39.0)
Interleukin-8, 0 hrs 189.8  (104.1) 248.9  (191.7)
Interleukin-8, 12 hrs 144  (133.4) 85.9  (59.9)
Interleukin-8, 24 hrs 101.5  (62.7) 139.2  (162.1)
Interleukin-8, 48 hrs 134.2  (107.0) 60.4  (33.7)
Tumor Necrosis Factor Preoperative 2.9  (0.8) 3.2  (1.1)
Tumor Necrosis Factor, 0 hrs 3.2  (1.5) 4.1  (1.6)
Tumor Necrosis Factor, 12 hrs 1.7  (0.07) 1.9  (1.1)
Tumor Necrosis Factor, 24 hrs 1.7  (1.3) 3.2  (2.9)
Tumor Necrosis Factor, 48 hrs 2.8  (0.09) 2.1  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitric Oxide Delivery Group, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments This p value applies to all time points for all variables.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Myocardial Injury
Hide Description Troponin levels correlate with myocardial injury. Greater troponin levels represent greater myocardial injury
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description:

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
Preoperative 0.07  (0.07) 0.06  (0.1)
0 h 50.6  (37.8) 54.1  (15.5)
12 h 11.7  (3.2) 15.9  (3.5)
24 h 8.9  (2.6) 12.5  (2.7)
48 h 4.8  (1.6) 7.6  (2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Treatment, 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments This applies for measurements at preoperative and 0 h time points.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Treatment, 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments This applies to measurements at time points 12 h, 24 h, and 48 h.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
3.Primary Outcome
Title Myocardial Function as Measured by B-type Natiuretic Peptide (BNP) Levels
Hide Description BNP levels correlate to ventricular and myocardial performance, function, and strain. Higher values represent greater strain and decreased function.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description:

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: pg/dL
Preoperative 24  (22) 100  (195)
0 h 43  (34) 94  (100)
12 h 494  (222) 812  (300)
24 h 425  (154) 938  (511)
48 h 558  (535) 1298  (827)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Treatment, 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments This applies to measurements at preoperative, 0 h, and 48 h time points.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1 Treatment, 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments This applies to time points at 12 h and 24 h.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Primary Outcome
Title Ischemic Injury as Measured by Lactate Levels
Hide Description Lactate levels correlate to ischemic injury. Higher values represent more injury.
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description:

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: mmol/L
Preoperative 0.9  (0.2) 0.5  (0.1)
0 h 1.9  (0.6) 1.9  (1.0)
12 h 1.5  (0.4) 1.5  (0.5)
24 h 1.4  (0.5) 1.4  (0.4)
48 h 1.1  (0.2) 1.1  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1 Treatment, 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments Applies to all time points.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Incidence of Methhemoglobin >5%, Gene Expression Profiles, and S100B.
Hide Description [Not Specified]
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Data not collected for these assessments
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description:

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were collected throughout the hospital admission or to 30 days postoperative; whichever is longer.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1 Treatment 2 Placebo
Hide Arm/Group Description

Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Nitric Oxide : Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.

Placebo delivery of oxygen at standard dose.
All-Cause Mortality
1 Treatment 2 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
1 Treatment 2 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
1 Treatment 2 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/8 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Paul Checchia MD
Organization: Baylor College of Medicine
Phone: 832-826-5011
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00585013     History of Changes
Other Study ID Numbers: CHECP1
First Submitted: December 20, 2007
First Posted: January 2, 2008
Results First Submitted: December 19, 2012
Results First Posted: November 4, 2015
Last Update Posted: November 4, 2015