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

Children's Hospital of Philadelphia (CHOP)

Status: Terminated

Conditions: Persistent Fetal Circulation Syndrome

Treatments: Drug: Milrinone Lactate

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01088997

09-007384

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 12 patients

Sex: All

Ages: Under 10 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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12 participants in 2 patient groups

High Dose Milrinone

Experimental group

Description:

Subjects will receive a bolus intravenous (IV) infusion of 50 mcg/kg/min of milrinone lactate over 1 hour followed by a continuous IV infusion of 0.5 mcg/kg/min milrinone lactate over 24 hours. After completion of infusion, subjects will be monitored for an additional 24 hours.

Treatment:

Drug: Milrinone Lactate

Low Dose Milrinone

Experimental group

Description:

Subjects will receive a bolus intravenous (IV) infusion of 20 mcg/kg/min of milrinone lactate over 1 hour followed by a continuous IV infusion of 0.2 mcg/kg/min milrinone lactate over 24 hours. After completion of infusion, subjects will be monitored for an additional 24 hours.

Treatment:

Drug: Milrinone Lactate