Iloprost-Study: Comparison of Nitric Oxide to Iloprost (Ventavis) for Treatment of Pulmonary Hypertension in Children After Cardiopulmonary Bypass Surgery

Investigators, Study Sites: Single-center trial at the Department of Pediatric Cardiology, Department of Cardiac Surgery and Department of Anesthesiology, University Medical Center, Heidelberg, Germany Exploratory proof of concept study (Investigator initiated trial)

Indication: Postoperative pulmonary hypertension in infants and children undergoing cardiopulmonary bypass surgery for intracardiac repair of left-to-right shunt

Objectives: To compare the efficacy of aerosolized iloprost with inhaled nitric oxide to prevent postoperative pulmonary hypertensive crises

Design: Exploratory, open label, randomized study with parallel-group design;

Duration of observation: 72 hours

Population: Infants older than 4 weeks and children less than 18 months of age presenting with left-to-right shunt and increased pulmonary blood flow. Inclusion will be independent on the presence or absence of preoperative pulmonary hypertension

Sample Size:

• 20 patients: inhaled nitric oxide (iNO) - group;
• 20 patients: aerosolized iloprost (ILO) -group

Treatment:

• Both groups: controlled ventilation, sedation, analgetics, inotropic substances as required, standardized intensive care treatment.
• iNO - group: concentration of iNO at 10 ppm; administered by mechanical ventilation.
• ILO - group: aerosolized Iloprost at a dose of 0,5 µg/kg body weight (12x / 24h), administered by ultrasound nebulizer.

Efficacy Parameters: Occurrence of "minor" or "major" pulmonary hypertensive crises (PHTC)

Safety Parameters: Arterial blood pressure, oxygen saturation, complete blood count

Statistical Procedures: All analyses in this exploratory trial are descriptive, giving confidence intervals for differences between treatment groups.

Primary analysis variable: Rate of occurrence of "major" or "minor" pulmonary hypertensive crises

Secondary variables: Presence of hours of pulmonary hypertension, Duration of mechanical ventilation

Inclusion criteria

• Informed consent by parents or legal representatives
• Age: Infants older than 4 weeks of age and children less than 1½ years of age.
• Presence of a left-to-right shunt with increased pulmonary blood flow. The specific defects that will be present are:

• Aortopulmonary (AP) - Window
• Atrioventricular septal defect (AVSD)
• Double outlet right ventricle (DORV)
• Total anomalous pulmonary venous drainage (TAPVD)
• Truncus arteriosus
• Ventricular septal defect (VSD)
• Presence of postoperative PH immediately after intracardiac repair:

• Patients will be enrolled if mean PAP after intracardiac repair exceeds 25 mmHg after weaning from CPB.

Exclusion criteria

• Specific cardiac defects:

• Atrial septal defect (ASD)
• Cyanotic congenital heart disease
• Univentricular atrio-ventricular - connexion
• Valvular or subvalvular pulmonary or aortic stenosis
• Specific circumstances:

• Emergency cardiac surgery
• Children presenting with infection after cardiac surgery
• Infants on extracorporeal membrane oxygenation (ECMO) before cardiac surgery
• Infants/children treated with epoprostenol
• Concomitant diseases:

• Systemic arterial hypertension
• Renal failure
• Diabetes mellitus
• Known bleeding disorders (known disorders of blood coagulation and hemostasis)
• Infection during the first 24 hours after cardiac surgery