Inhaled NO as an Anti-inflammatory and Anti-reperfusion Agent in Infants and Children Undergoing Cardiopulmonary Bypass

NCT00585013 | Completed Phase 1 Results DMC

• 1 other identifier: CHECP1
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Heart Disease

Keywords

Inhaled Nitric Oxide (NO); Anti-inflammatory; Anti-reperfusion agent

Outcome Measures

Primary Outcomes (4)

• Serum Inflammatory Mediators Post CPB

  Inflammation measured through the measurement inflammatory mediators, serum interleukin-6, serum interleukin-8, and tumor necrosis factor. Baseline (preoperative, 0h, 12h, 24h, and 48h.

  48 hours

• Myocardial Injury

  Troponin levels correlate with myocardial injury. Greater troponin levels represent greater myocardial injury

  48 hours

• Myocardial Function as Measured by B-type Natiuretic Peptide (BNP) Levels

  BNP levels correlate to ventricular and myocardial performance, function, and strain. Higher values represent greater strain and decreased function.

  48 hours

• Ischemic Injury as Measured by Lactate Levels

  Lactate levels correlate to ischemic injury. Higher values represent more injury.

  48 hours

Secondary Outcomes (1)

• Incidence of Methhemoglobin >5%, Gene Expression Profiles, and S100B.

  48 hours

Study Arms (2)

Nitric Oxide Delivery Group

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.

Drug: Nitric Oxide

Placebo

NO INTERVENTION

Placebo delivery of oxygen at standard dose.

Interventions

Nitric Oxide DRUG

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.

Also known as: NO gas

Nitric Oxide Delivery Group

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients with the following congenital heart lesions who require cardiopulmonary bypass for surgical repair or palliation will be eligible:
• D-transposition of the great vessels (D-TGA)
• Tetralogy of Fallot (TOF)
• Children of age less than 16 years

You may not qualify if:

• Signs of persistently elevated pulmonary vascular resistance preoperatively
• Cardiac arrest one week prior to surgery
• Prior surgical procedure that required use of cardio-pulmonary bypass
• Acute or chronic infection such as sepsis or wound infections
• History of any pulmonary condition such as pneumonia or respiratory distress syndrome
• Patients that have received steroid treatment within the last month
• DiGeorge syndrome
• Active bleeding disorder
• Any other condition associated with non-cardiac morbidity
• Use of another investigational drug
• Age over 16 years.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Mallinckrodt: collaborator

Study Sites (1)

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children--a randomized trial. J Thorac Cardiovasc Surg. 2013 Sep;146(3):530-6. doi: 10.1016/j.jtcvs.2012.09.100. Epub 2012 Dec 8.

  PMID: 23228403 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital

Interventions

Nitric Oxide

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Reactive Nitrogen Species; Free Radicals; Inorganic Chemicals; Nitrogen Oxides; Nitrogen Compounds; Oxides; Oxygen Compounds; Organic Chemicals

Results Point of Contact

• Title: Paul Checchia MD
• Organization: Baylor College of Medicine

checchia@bcm.edu

832-826-5011

Study Officials

• Paul Checchia, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: January 2, 2008
• Study Start: January 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: November 4, 2015
• Results First Posted: November 4, 2015

Record last verified: 2015-11

Locations

US (1)