Pharmacokinetic Study of Milrinone in Babies With Persistent Pulmonary Hypertension of the Newborn

Milrinone Pharmacokinetics and Pharmacodynamics in Newborns With Persistent Pulmonary Hypertension of the Newborn - a Pilot Study to Enable a Randomized Trial of Intervention

The purpose of this pilot study is to determine a safe dose of milrinone to use in a larger study of babies with persistent pulmonary hypertension of the newborn (PPHN).

Persistent pulmonary hypertension of the newborn (PPHN) is a condition in which the pulmonary vasculature fails to relax after birth resulting in severe hypoxemia. This condition has a high rate of mortality and morbidity. The current standard of care is treatment with inhaled nitric oxide (iNO). However, for many babies this treatment does not provide sufficient improvement in oxygenation.

In this study, subjects already receiving nitric oxide will be randomized to one of two dosing regimens of milrinone. They will receive milrinone IV for 24 hours and will be monitored for 24 hours afterwards. During this time, milrinone assays will be performed by blood sampling. Echocardiograms will also be performed to explore the pharmacodynamics of milrinone. Safety monitoring will be performed.

Inclusion Criteria:

• Gestational age > 34 weeks
• Post-natal age < 10 days
• Hypoxemia defined by: Oxygenation Index (OI) >15 (Mean Airway Pressure x Fraction of Inspired Oxygen (FiO2) 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 >75% 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 extracorporeal membrane oxygenation (ECMO)or plan to initiate ECMO within 2 hours of enrollment