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Trial record 1 of 1 for:    NCT02151877
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Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass

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ClinicalTrials.gov Identifier: NCT02151877
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : April 3, 2020
Last Update Posted : April 3, 2020
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Chawki Elzein, Advocate Health Care

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.


Condition or disease Intervention/treatment Phase
Ischemia/Reperfusion Injury After Neonatal Cardiac Surgery Inflammatory Reaction After Neonatal Cardiac Surgery Drug: Inhaled Nitric Oxide Drug: placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass.
Study Start Date : July 2014
Actual Primary Completion Date : August 15, 2018
Actual Study Completion Date : August 15, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nitric oxide on CPB
neonates receiving inhaled NO into the cardiopulmonary bypass circuit during cardiac surgery
Drug: Inhaled Nitric Oxide
delivering inhaled Nitric Oxide into the cardiopulmonary bypass circuit during neonatal cardiac surgery
Other Name: study group

Placebo Comparator: control
neonates not receiving inhaled NO into the cardiopulmonary bypass
Drug: placebo
inhaled Nitric Oxide not delivered to the cardiopulmonary bypass circuit during neonatal cardiac surgery
Other Name: control group




Primary Outcome Measures :
  1. Change in Biochemical Markers of Ischemia/Reperfusion Injury and Oxidative Damage (Positive ~ Increase From Pre-op) [ Time Frame: 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 :
  1. Total Fluid Balance at 48 Hours [ Time Frame: 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.

  2. Time Until Start of Diuretic Therapy [ Time Frame: Pre-op to 72 hours post surgery ]
    hours until start of diuretic therapy

  3. Inotropic Score Day 1 [ Time Frame: 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 )


  4. Length of Intubation and PSHU Stay [ Time Frame: Surgery to discharge ]
    Days to extubation and Pediatric Surgical Heart Unit (PSHU) length of stay (LOS) as measuring patient surgical outcomes.


Other Outcome Measures:
  1. Surgical Morbidity [ Time Frame: 1 month after cardiac surgery ]
    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..



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Ages Eligible for Study:   up to 30 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02151877


Locations
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United States, Illinois
Advocate Children's Hospital
Oak Lawn, Illinois, United States, 60453
Sponsors and Collaborators
Chawki Elzein
Mallinckrodt
Investigators
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Principal Investigator: Chawki F Elzein, MD Advocate Healthcare
  Study Documents (Full-Text)

Documents provided by Chawki Elzein, Advocate Health Care:

Additional Information:
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Responsible Party: Chawki Elzein, Associate clinical Professor, Advocate Health Care
ClinicalTrials.gov Identifier: NCT02151877    
Other Study ID Numbers: K5900209
First Posted: June 2, 2014    Key Record Dates
Results First Posted: April 3, 2020
Last Update Posted: April 3, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Chawki Elzein, Advocate Health Care:
Ischemia/reperfusion injury
Additional relevant MeSH terms:
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Reperfusion Injury
Ischemia
Inflammation
Wounds and Injuries
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents