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Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet Activation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03455218
Recruitment Status : Completed
First Posted : March 6, 2018
Results First Posted : August 13, 2020
Last Update Posted : August 13, 2020
Sponsor:
Collaborators:
Mallinckrodt
Clinical & Translational Science Institute of Southeast Wisconsin
Versiti
Information provided by (Responsible Party):
Robert Niebler, MD, Medical College of Wisconsin

Brief Summary:
Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. This reaction is intensified in younger, smaller patients undergoing longer, more complex open heart surgery. Nitric oxide is naturally released by vascular endothelial surfaces and acts as a signaling molecule which prevents platelet activation. The investigators hypothesize that the addition of the nitric oxide to the sweep gas of the oxygenator during cardiopulmonary bypass surgery will replace this natural endothelial function and thus prevent platelet activation and consumption. The investigators plan to test this hypothesis with a pilot double blinded, randomized trial of 40 patients less than a year of age undergoing cardiac surgery requiring CPB.

Condition or disease Intervention/treatment Phase
Inflammation Platelet Dysfunction Drug: Nitric Oxide Drug: Placebo Device: INOmax Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double Blinded, Placebo Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet activation-a Single Center Pilot Study
Actual Study Start Date : April 25, 2018
Actual Primary Completion Date : April 20, 2019
Actual Study Completion Date : May 5, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nitric Oxide
20 ppm of Nitric Oxide delivered to the oxygenator via the INOmax device for the duration of the cardiopulmonary bypass time
Drug: Nitric Oxide
20 ppm of Nitric Oxide gas delivered to the oxygenator for the duration of cardiopulmonary bypass
Other Name: INOmax

Device: INOmax
All patients will have the INOmax device connected to the oxygenator
Other Name: inhaled nitric oxide delivery device

Placebo Comparator: Placebo
INOmax device attached to the oxygenator, but no gas is delivered through the device
Drug: Placebo
INOmax device connected to oxygenator, but no gas is delivered

Device: INOmax
All patients will have the INOmax device connected to the oxygenator
Other Name: inhaled nitric oxide delivery device




Primary Outcome Measures :
  1. Change in Platelet Count [ Time Frame: From baseline to end of cardiopulmonary bypass (2-6 hours) ]
    Change in platelet count from baseline to conclusion of cardiopulmonary bypass = (Platelet count at end of CPB) - (Platelet count prior to start of CPB)

  2. 30 Day Mortality [ Time Frame: 30 days ]
    30 day all cause mortality

  3. Hospital Length of Stay [ Time Frame: 6 months ]
    Length of stay in the hospital following the operation

  4. Methemoglobin Level Pre-CPB [ Time Frame: 24 hours ]
    Methemoglobin levels in the blood measured at baseline

  5. Methemoglobin Level-End of CPB [ Time Frame: 4 hours ]
    Methemoglobin Level obtained at the end of cardiopulmonary bypass

  6. Methemoglobin Level-ICU Admit [ Time Frame: 24 hours ]
    Methemoglobin level obtained at the time of ICU Admit


Secondary Outcome Measures :
  1. Change in Platelet Response to TRAP as Measured by P-selectin Expression [ Time Frame: From baseline to end of cardiopulmonary bypass (2-6 hours) ]
    The P-selectin expression measured as a mean florescence was measured in platelets stimulated with thrombin receptor activating protein (TRAP) was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to TRAP at end of CPB) - (Platelet response to TRAP prior to CPB)

  2. Change in Platelet Response to U46619 as Measured by P-selectin Expression [ Time Frame: From baseline to end of cardiopulmonary bypass (2-6 hours) ]
    The P-selectin expression measured as a mean florescence was measured in platelets stimulated with U46619 was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to U46619 at end of CPB) - (Platelet response to U46619 prior to CPB)

  3. Change in Platelet Response to CRP as Measured by P-selectin Expression [ Time Frame: From baseline to end of cardiopulmonary bypass (2-6 hours) ]
    The P-selectin expression measured as a mean florescence was measured in platelets stimulated with CRP was measured at baseline and at conclusion of cardiopulmonary bypass. Mean of each assessment measured multiple times at each time point. Median change values were reported. The change in these values is the outcome measure = (Platelet response to CRP at end of CPB) - (Platelet response to CRP prior to CPB)

  4. Volume of Platelet Transfusion [ Time Frame: 48 hours post-operatively ]
    Volume per kg of platelet transfusion given to patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively

  5. Volume of Packed Red Blood Cell Transfusion [ Time Frame: 48 hours post-operatively ]
    Volume per kg of packed red blood cell transfusion given to patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively

  6. Transfusion Exposures [ Time Frame: 48 hours post-operatively ]
    Total number of transfusion exposures for a patient from the conclusion of cardiopulmonary bypass to 48 hours post-operatively

  7. Length of Mechanical Ventilation [ Time Frame: 30 days post-operatively ]
    Time (days) spent on ventilator following the operation

  8. Vasoactive Infusion Score [ Time Frame: 24 hours post-operatively ]

    Highest vasoactive infusion score (VIS) within 24 hours post-operatively. Vasoactive infusion score is based on the dose of the vasoactive infusions the patient is given VIS = Dopamine dose (μg/kg/min) + Dobutamine dose (μg/kg/min) +100 × epinephrine dose (μg/kg/min) + 10 X Milrinone dose (μg/kg/min) +10,000 × Vasopressin dose (U/kg/min) + 100 × Norepinephrine dose (μg/kg/min).

    The minimum value is 0 if the patient is not on any vasoactive medications. There is no "maximum" score as there is no "maximum" dose of vasoactive medications. Higher scores indicate that the patient is on more vasoactive medications which is generally considered worse.


  9. Number of Subjects Requiring Extracorporeal Membrane Oxygenation [ Time Frame: 48 hours post-operatively ]
    Dichotomous outcome-required extracorporeal membrane oxygenation within 48 hours post-operatively

  10. Hospital Cost [ Time Frame: 6 months post-operatively ]
    Total hospital cost at the time of discharge



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 1 Year   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants less than one year of age
  • Undergoing cardiac surgery with the use of cardiopulmonary bypass

Exclusion Criteria:

  • Prior surgery requiring CPB within the same hospitalization
  • Pre-operative need for extracorporeal membrane oxygenation or mechanical circulatory support
  • Known hypersensitivity to nitric oxide
  • Known hemostatic or thrombotic disorder that results in an altered transfusion/anticoagulation protocol

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): NCT03455218


Locations
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United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Mallinckrodt
Clinical & Translational Science Institute of Southeast Wisconsin
Versiti
  Study Documents (Full-Text)

Documents provided by Robert Niebler, MD, Medical College of Wisconsin:
Publications:

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Responsible Party: Robert Niebler, MD, Associate Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT03455218    
Other Study ID Numbers: 1111115-1NO in CPB 001
First Posted: March 6, 2018    Key Record Dates
Results First Posted: August 13, 2020
Last Update Posted: August 13, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: we are willing to share the IPD if requested by another investigator. Please contact the principle investigator if interested

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Robert Niebler, MD, Medical College of Wisconsin:
Cardiopulmonary Bypass
Infant
Nitric Oxide
Thrombocytopenia
Blood Platelets
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes
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