Trial Outcomes & Findings for Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass (NCT NCT02151877)

Last Updated: 2024-10-08

Results Overview

The primary study endpoints are to evaluate whether NO delivered through the neonatal cardiopulmonary bypass (CPB) circuit can decrease various biochemical markers of ischemia/reperfusion injury and oxidative damage. Markers to be analyzed will include cardiac troponin I, interleukins (IL), tumor necrosis factor, N-terminal prohormone for brain natriuretic peptide (NT-proBNP),lactate dehydrogenase (LDH), plasma anti-oxidant levels, plasma malondialdehyde (MDA) levels.

Recruitment status

COMPLETED

Study phase

Target enrollment

24 participants

Primary outcome timeframe

Pre-op baseline and up to 12 hours after surgery

Results posted on

2024-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Nitric Oxide on CPB neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Total n=24 Participants Total of all reporting groups	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Age, Categorical <=18 years	12 Participants n=7 Participants	24 Participants n=5 Participants	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Age, Continuous	5.92 days STANDARD_DEVIATION 1.78 • n=7 Participants	5.79 days STANDARD_DEVIATION 1.82 • n=5 Participants	5.67 days STANDARD_DEVIATION 1.87 • n=5 Participants
Sex: Female, Male Female	5 Participants n=7 Participants	9 Participants n=5 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=7 Participants	15 Participants n=5 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=7 Participants	19 Participants n=5 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=7 Participants	24 participants n=5 Participants	12 participants n=5 Participants
anatomical diagnosis, hypoplastic left heart syndrome	11 Participants n=7 Participants	21 Participants n=5 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-op baseline and up to 12 hours after surgery

Population: Intent to treat (ITT)

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) IL-8 change	49.36 ng/ml Standard Deviation 42.86	68.46 ng/ml Standard Deviation 81.09
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) cardiac troponin I change	0.46 ng/ml Standard Deviation 0.55	0.64 ng/ml Standard Deviation 0.64
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) LDH change	48.85 ng/ml Standard Deviation 117.39	53.44 ng/ml Standard Deviation 73.58
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) IL-6 change	11.52 ng/ml Standard Deviation 12.98	26.98 ng/ml Standard Deviation 27.67
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) TNF alpha change	0.03 ng/ml Standard Deviation 0.20	-0.12 ng/ml Standard Deviation 0.21
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) NT pro-BNP change	7.03 ng/ml Standard Deviation 22.84	1.51 ng/ml Standard Deviation 2.29
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) Superoxide Dismutase change	-0.04 ng/ml Standard Deviation 0.04	-0.05 ng/ml Standard Deviation 0.06
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) Plasma MDA change	7.61 ng/ml Standard Deviation 12.90	10.65 ng/ml Standard Deviation 14.99

SECONDARY outcome

Timeframe: 48 hours post surgery

Population: Intent to treat

The secondary study endpoints are to evaluate whether NO delivered through the neonatal CPB circuit can decrease the clinical signs of ischemia/reperfusion injury and/or cardiac dysfunction. Clinical parameters (post surgery) include inotropic support, fluid balances, diuretic support, ventilator times, and length of ICU stay will be evaluated.

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Total Fluid Balance at 48 Hours	32.24 ml/kg Interval -52.9 to 165.26	15.93 ml/kg Interval -160.55 to 73.245

SECONDARY outcome

Timeframe: Pre-op to 72 hours post surgery

Population: Intent to treat

hours until start of diuretic therapy

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Time Until Start of Diuretic Therapy	25 hour Interval 22.5 to 30.25	21.5 hour Interval 19.25 to 24.0

SECONDARY outcome

Timeframe: 24 hours post surgery

Population: ITT

The Inotropic Score is an objective clinical tool used to quantify the need for cardiovascular support in children and adolescents after surgery and to predict prognosis of pediatric septic shock (higher score predicts higher risk or worse prognosis).The Inotropic Score is low if \<= 20, intermediate if 21-30, and high if \> 30. Formula used in the study: Daily inotropic score (mcg/kg/min) = Dopamine drip dose+ dobutamine drip dose+ (milrinone drip dose times 10) + (epinephrine drip dose times 100 )

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Inotropic Score Day 1	16.5 mcg/kg/min Interval 12.75 to 19.75	15 mcg/kg/min Interval 13.5 to 18.75

SECONDARY outcome

Timeframe: Surgery to discharge

Population: ITT

Days to extubation and Pediatric Surgical Heart Unit (PSHU) length of stay (LOS) as measuring patient surgical outcomes.

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Length of Intubation and PSHU Stay Days to extubation	7.5 days Interval 6.25 to 9.5	6.5 days Interval 5.25 to 14.75
Length of Intubation and PSHU Stay PSHU Length of Stay (LOS)	15 days Interval 10.5 to 22.25	12 days Interval 11.0 to 15.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 month after cardiac surgery

Population: Intent to treat

include all complications that may happen after cardiac surgery for the whole period of hospital stay, that is expected to be around 1 month. This include renal failure, prolonged intubation and ventilatory support, infections..

Outcome measures

Outcome measures
Measure	Nitric Oxide on CPB n=12 Participants neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery Inhaled Nitric Oxide: delivered inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period	Control n=12 Participants neonates not receiving inhaled NO into the cardiopulmonary bypass placebo: inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery 12 patients were enrolled prospectively over 4 years period
Surgical Morbidity	0 Participants	0 Participants

Adverse Events

Nitric Oxide on CPB

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Control

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nitric Oxide on CPB n=12 participants at risk Group that received nitric oxide in CPB	Control n=12 participants at risk Group that did not receive nitric oxide in CPB
Blood and lymphatic system disorders Chylothorax	8.3% 1/12 • Number of events 1 • Adverse events (AEs) were collected for the entire hospitalization period, from surgical date to 104 days.	0.00% 0/12 • Adverse events (AEs) were collected for the entire hospitalization period, from surgical date to 104 days.
Cardiac disorders needed cath intervention	8.3% 1/12 • Number of events 1 • Adverse events (AEs) were collected for the entire hospitalization period, from surgical date to 104 days.	8.3% 1/12 • Number of events 1 • Adverse events (AEs) were collected for the entire hospitalization period, from surgical date to 104 days.

Additional Information

Chawki Elzein, MD, FACS

Advocate Health Care

Phone: 7086843029

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place