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

NCT02151877 | Completed Results DMC

• 1 other identifier: K5900209
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery; Inflammatory Reaction After Neonatal Cardiac Surgery

Keywords

Ischemia/reperfusion injury

Outcome Measures

Primary Outcomes (1)

• Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op)

  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.

  Pre-op baseline and up to 12 hours after surgery

Secondary Outcomes (4)

• Total Fluid Balance at 48 Hours

  48 hours post surgery

• Time Until Start of Diuretic Therapy

  Pre-op to 72 hours post surgery

• Inotropic Score Day 1

  24 hours post surgery

• Length of Intubation and PSHU Stay

  Surgery to discharge

Other Outcomes (1)

• Surgical Morbidity

  1 month after cardiac surgery

Study Arms (2)

Nitric oxide on CPB

EXPERIMENTAL

neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery

Drug: Inhaled Nitric Oxide

control

PLACEBO COMPARATOR

neonates not receiving inhaled NO into the cardiopulmonary bypass

Drug: placebo

Interventions

Inhaled Nitric Oxide DRUG

delivering inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery

Also known as: study group

Nitric oxide on CPB

placebo DRUG

inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery

Also known as: control group

control

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Mallinckrodt: collaborator

Study Sites (1)

Advocate Children's Hospital

Oak Lawn, Illinois, 60453, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Ischemia; Reperfusion Injury

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Results Point of Contact

• Title: Chawki Elzein, MD, FACS
• Organization: Advocate Health Care

chawki.elzein@advocatehealth.com

7086843029

Study Officials

• Chawki F Elzein, MD

  Advocate Healthcare

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2014
• First Posted: June 2, 2014
• Study Start: July 1, 2014
• Primary Completion: August 15, 2018
• Study Completion: August 15, 2018
• Last Updated: October 8, 2024
• Results First Posted: April 3, 2020

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)