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

Not Applicable

Completed

• Conditions: Inflammatory Reaction After Neonatal Cardiac Surgery; Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery
• Interventions: Drug: Inhaled Nitric Oxide; Drug: placebo

• Registration Number: NCT02151877
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

Around 7500 neonates born yearly in the United States have complex congenital heart disease that require surgical repair in the first few days of life. The complexity of the surgical repair requires long periods of cardiopulmonary bypass (CPB) and the use of intermittent periods of low flow or complete circulatory arrest. The immature neonatal vital organs are more prone to the complications of the cardiopulmonary bypass circulation, namely ischemia/reperfusion (I/R) injury and systemic inflammatory response. Inhaled nitric oxide (NO) is used frequently in neonates for the treatment of pulmonary hypertension, Additionally, many studies have shown that NO has an anti-inflammatory effect by reducing I/R injury and endothelial dysfunction.

The purpose of this pilot study is to assess the efficacy of NO administration via the CPB circuit in attenuating the CPB induced I/R injury and systemic inflammatory reaction in neonates undergoing repair of complex congenital heart defects. Specific goals will be to demonstrate that NO use via CPB will:

* Decrease markers of I/R injury and systemic inflammatory response.

* Decrease platelet activation leading to reduced postoperative bleeding and transfusion requirements.

* Decrease postoperative organ dysfunction, and hence decrease operative mortality and postoperative morbidity.

Twelve neonates undergoing repair of complex congenital heart defects will receive NO via the CPB circuit, for the duration of surgery. They will be compared to a control group of 12 similar patients. Serum levels of different ischemic reperfusion injury and inflammatory markers will be measured at different time points after surgery and will be correlated with different end organ function tests and clinical course in the postoperative period. The results will be compared between the two groups to try to determine the clinical benefit of NO administration through CPB circuit.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-05-27
• Study First Submitted QC: 2014-05-28
• Study First Posted: 2014-06-02
• Study Start: 2014-07
• Primary Completion: 2018-08-15
• Study Completion: 2018-08-15
• Results First Submitted: 2019-10-30
• Results First Submitted QC: 2020-04-02
• Results First Posted: 2020-04-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Neonates, age 0-30 days
• Full term, > 37 weeks gestation
• Birth weight ≥ 2.6 kg

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Exclusion Criteria

• Preoperative sepsis
• Preoperative renal dysfunction
• Preoperative intracranial hemorrhage
• Chromosomal abnormalities and/or genetic syndromes
• Prior intervention (catheter based or surgical)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitric oxide on CPB	Inhaled Nitric Oxide	neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery
control	placebo	neonates not receiving inhaled NO into the cardiopulmonary bypass

Primary Outcome Measures

Name	Time	Method
Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op)	Pre-op baseline and up to 12 hours after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Total Fluid Balance at 48 Hours	48 hours post surgery	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.
Time Until Start of Diuretic Therapy	Pre-op to 72 hours post surgery	hours until start of diuretic therapy
Inotropic Score Day 1	24 hours post surgery	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 )
Length of Intubation and PSHU Stay	Surgery to discharge	Days to extubation and Pediatric Surgical Heart Unit (PSHU) length of stay (LOS) as measuring patient surgical outcomes.

Trial Locations

Locations (1)

Advocate Children's Hospital; 🇺🇸 Oak Lawn, Illinois, United States