Newborns with congenital diaphragmatic hernia: inhaled nitric oxide versus intravenous sildenafil: an international randomized controlled trial

INTERVENTION: Sildenafil with be given intravenously, using a loading dose of 0.4mg/kg in 3 hours, followed by continuous infusion of 1.6mg/kg/day Inhaled NO will be given with a starting dose of 20 ppm, which is the maximum dose CONDITION: Congenital diaphragmatic hernia, Pulmonary arterial hypertension (PAH), Infant‐newborn ; ; PRIMARY OUTCOME: The absence of pulmonary hypertension on echocardiography on day 14 without pulmonary vasodilator therapy and without treatment failure in patients and/or death within the first 28 days of life SECONDARY OUTCOME: • Oxygenation index ; ; • Overall mortality ; ; • Incidence of treatment failure ; ; • Time on intervention drug (intervention drug free days on day 14) ; ; • Vasoactive‐inotropic support score ; ; • Need for ECMO ; ; • Ventilator free days on day 28 ; ; • Severity of pulmonary hypertension, using laboratory markers and tracheal aspirates for proteomic, metabolomics and biochemical analysis as a marker ; ; • The use of other medication given for pulmonary hypertension during the hospital admission ; ; • The use of pulmonary and/or cardiac medication at discharge and its total duration ; ; • Long‐term pulmonary hypertension on echocardiography at 6 and 12 months ; ; • Chronic lung disease ; ; • The development of neurological abnormalities evaluated with ultrasound of the brain ; ; • External validation of sildenafil PKPD model ; INCLUSION CRITERIA: Diagnosis of CDH and pulmonary hypertension defined as 2 of the following 4 criteria: I. Systolic PAP> 2/3 systemic systolic pressure estimated by echocardiography II. RV dilatation/septal displacement, RV dysfunction +/‐ LV dysfunction III. Pre‐post ductal SpO2 difference > 10% IV. OI>20. Parental informed consent Children born at or after a gestational age of 34 weeks Newborns who received a fetal intervention may be included