Kirpalani

Trial name or title	Milrinone Pharmacokinetics and Pharmacodynamics in Newborns With Persistent Pulmonary Hypertension of the Newborn ‐ a Pilot Study to Enable a Randomized Trial of Intervention
Methods	Allocation: randomized Endpoint classification: pharmacokinetics/dynamics study Intervention model: parallel assignment Masking: single blind (outcomes assessor)
Participants	Inclusion criteria: Gestational age > 34 weeks Birth weight of > 2500g Post‐natal age < 10 days Hypoxemia defined by: Oxygenation Index (OI) >20 (mean airway pressure x fraction of inspired oxygen x 100 /PaO2) as drawn from two post‐ductal arterial blood gas samples (in‐dwelling arterial catheter) taken at least 15 minutes apart OR mechanically ventilated and with > 90% FiO2 for > 6 hours while on iNO Absence of congenital heart disease based on a two‐dimensional echocardiogram and/or clinical assessment An in‐dwelling arterial catheter to facilitate painless sampling Currently on iNO or plan to start iNO before enrollment Exclusion criteria: Lethal non‐cardiac congenital anomalies including diaphragmatic hernia Clinically apparent bleeding; thrombocytopenia < 30,000 or other laboratory evidence of coagulopathy Currently on ECMO or plan to initiate ECMO within 2 hours of enrollment
Interventions	Milrinone lactate High dose: experimental 50 mcg/kg load followed by 0.5 mcg/kg/min infusion Low dose: experimental 20 mcg/kg load followed by 0.2 mcg/kg/min infusion
Outcomes	Primary: pharmacokinetic profile of milrinone in newborns with PPHN Secondary: oxygenation index echocardiographic signs of pulmonary hypertension (parameters measured will be: myocardial performance index (MPI) of LV and RV, cardiac output of LV, tricuspid regurgitation (trivial, mild, moderate, severe), RV systolic pressure, mitral regurgitation (trivial, mild, moderate, severe), presence or absence of patent foramen ovale (PFO) with peak and mean pressure gradient, and presence or absence of patent ductus arteriosus (PDA) with peak and mean pressure gradient) safety profile: safety analysis will be performed as follows: blood pressure will be monitored hourly for 48 hours, platelet count will be measured daily, cardiac rhythm will be monitored continuously for 48 hours, renal function will be monitored daily, and liver transaminases will be monitored within a week. All adverse events will be included in the safety analysis
Starting date	April 2010
Contact information	ClinicalTrials.gov identifier: NCT01088997
Notes	The Children's Hospital of Philadelphia; Pennsylvania Hospital