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Sponsors and Collaborators: |
Washington University School of Medicine INO Therapeutics |
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Information provided by: | Washington University School of Medicine |
ClinicalTrials.gov Identifier: | NCT00585013 |
Each year, there are over 400,000 cardiac surgical operations performed in the United States; of which 10,000 are performed on children. These operations are made possible by the use of the heart-lung bypass machine, also known as cardiopulmonary bypass. This machine allows for the body to be supported while the heart is repaired. While this machine has been life saving, it has risks and can lead to a variety of complications.
One such complication results from the fact that the patient's blood is exposed to the foreign material of the machine, such as plastic tubing. In nearly all cases of cardiac surgery, this leads to a whole body response in the patient following the operation. This response, inflammation, is characterized by alterations in the function of the heart and lungs, fever, fluid retention, and bleeding disorders in the postoperative period. While this is usually temporary and self limiting, significant morbidity occurs in approximately 1-2% of cases where this inflammatory response is present.
Additionally, children appear to be more susceptible to this response. This can lead to significant postoperative complications that are not associated with the actually surgical procedure performed on the heart.
The exact cause of this response is not fully understood. However, it is important to understand the triggers, timing, and pattern of this complex inflammatory response in order to modify or arrest it. Unlike other situations associated with this type of whole-body inflammatory reaction such as trauma or overwhelming infection, cardiac surgical teams have the advantage of knowing when the trigger will occur (i.e. during the cardiac operation) and hence have the opportunity for preemptive intervention in an effort to minimize the response. One such effort is the focus of this proposal.
Nitric oxide (NO) is a gas that has been used for years in the treatment of lung disease in infants. It has been life saving and safe. Recently, it has been investigated for its anti-inflammatory effects outside the lungs. We propose delivering NO to the source of the greatest inflammation in cardiac surgery, the cardiopulmonary bypass machine. It is our intention to show that in doing so; we can minimize the inflammation found in the first 24 hours following cardiac surgery in children. If we are correct, the reduction of this inflammation will result in less damage to other organs of the child's body and improved outcome following surgery.
Condition | Intervention | Phase |
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Congenital Heart Disease Systemic Inflammatory Response |
Drug: Nitric Oxide |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Trial of Inhaled Nitric Oxide (NO) as an Anti-Inflammatory and Anti-Reperfusion Agent in the Treatment of Infants and Children Undergoing Cardiopulmonary Bypass for Repair of Congenital Heart Disease |
Estimated Enrollment: | 30 |
Study Start Date: | January 2008 |
Estimated Study Completion Date: | July 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.
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Drug: Nitric Oxide
Patients will receive standard care with the addition of NO gas. During cardiopulmonary bypass, NO at 20 ppm will be added to the sweep gas of the extracorporeal circuit. Following termination of cardiopulmonary bypass, inhaled NO will be discontinued.
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2: No Intervention
Placebo delivery of oxygen at standard dose.
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I. Hypothesis Treatment of children during surgery employing cardiopulmonary bypass with inhaled, exogenous nitric oxide (iNO) delivered to the cardiopulmonary bypass circuit will:
II. Specific Aims
Three specific aims will test this hypothesis:
Delivery of iNO to the cardiopulmonary bypass circuit will result in a decrease in:
III. Introduction and Background
IV. Basic Protocol Experimental Design In a prospective, randomized, controlled, blinded pilot trial we will compare 20 ppm of iNO delivered to the CPB circuit. Our study will target children undergoing cardiopulmonary bypass (CPB) for surgery for the correction of transposition of great arteries (TGA) and Tetralogy of Fallot (TOF).
Subjects Inclusion Undergoing repair of TGA and TOF < 16 years of age Exclusion Age > 16 years of age Pregnancy Known bleeding disorder
Treatment Protocol Following informed consent, blood will be drawn pre-operatively for baseline characteristics (methemoglobin, venous saturation, CBC, S100, gene expression profiles, BNP, cTnI, IL-6, IL-8, lactate, TNFalpha)[Table, Blood sample for Study]. Intra-operatively we will use a standardized anesthetic protocol unless contraindicated by specific patient clinical characteristics. Intraoperative measurements will include: aortic cross clamp time, and total cardiopulmonary bypass time. Intraoperative hemodynamic measurements will include: mean systemic blood pressure (MAP), central venous pressure, right atrial pressure pulmonary artery pressure, and pulmonary capillary wedge pressure (when available). Blood samples will be drawn following CPB upon arrival to the ICU and will be analyzed as above. Repeat blood samples for each will be drawn again after 12, 24, and 48 hours. Patients will be followed to the time of discharge. Ventilator settings, length of ICU and hospital stay will be recorded. All measurements in both groups will be the same. Time points will be referenced from the time of admission to the PICU for both groups.
Ages Eligible for Study: | up to 16 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, Missouri | |
St. Louis Children's Hospital | Recruiting |
St. Louis, Missouri, United States, 63110 | |
Contact: Paul A Checchia, MD 314-454-2527 pchecchia@wustl.edu | |
Principal Investigator: Paul A Checchia, MD |
Responsible Party: | Washington University School of Medicine ( Paul A. Checchia MD ) |
Study ID Numbers: | CHECP1 |
Study First Received: | December 20, 2007 |
Last Updated: | December 10, 2008 |
ClinicalTrials.gov Identifier: | NCT00585013 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Inhaled Nitric Oxide (NO) Anti-inflammatory Anti-reperfusion agent |
Nitric Oxide Vasodilator Agents Neurotransmitter Agents Antioxidants Heart Diseases Cardiovascular Abnormalities |
Anti-Asthmatic Agents Cardiovascular Agents Peripheral Nervous System Agents Congenital Abnormalities Bronchodilator Agents Heart Defects, Congenital |
Respiratory System Agents Vasodilator Agents Neurotransmitter Agents Antioxidants Heart Diseases Molecular Mechanisms of Pharmacological Action Cardiovascular Abnormalities Physiological Effects of Drugs Anti-Asthmatic Agents Cardiovascular Agents Protective Agents |
Pharmacologic Actions Nitric Oxide Autonomic Agents Therapeutic Uses Free Radical Scavengers Endothelium-Dependent Relaxing Factors Cardiovascular Diseases Peripheral Nervous System Agents Congenital Abnormalities Heart Defects, Congenital Bronchodilator Agents |