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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Comparison of Inhaled Nitric Oxide With Aerosolized Iloprost (Ventavis®) for Treatment of Pulmonary Hypertension in Children After Cardiopulmonary Bypass Surgery

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: aerosolized iloprost


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: aerosolized iloprost|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of pulmonary hypertensive crises (major and/or minor) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment with aerosolized ILO is equally effective as iNO in reducing the pulmonary artery pressure (PAP) within the first 72 hours after cardiopulmonary bypass surgery (CPB) |  |  | 
| Patients treated with aerosolized ILO can be weaned earlier from mechanical ventilation than patients on iNO treatment |  |  | 
| Patients treated with aerosolized ILO show the same in-hospital mortality as patients treated with iNO |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary hypertension, Cardiac Surgery, Children, Pediatric Patients, Iloprost, NO, nitric oxide, Pulmonary hypertension after cardiac surgery in pediatric patients, 0 - 2 years old