Iloprost-Study: Comparison of Nitric Oxide to Iloprost (Ventavis) for Treatment of Pulmonary Hypertension in Children After Cardiopulmonary Bypass Surgery
Iloprost-Study: Comparison of Nitric Oxide to Iloprost (Ventavis) for Treatment of Pulmonary Hypertension in Children After Cardiopulmonary Bypass Surgery
Inhaled nitrous oxide (iNO) will be compared to aerosolized iloprost (ILO) in pediatric
 patients after cardiac surgery with pulmonary hypertension. The hypothesis is that iloprost
 is more effective in preventing pulmonary hypertensive crises.
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