Clinical trial NCT01088997: Pharmacokinetic Study of Milrinone in Babies With Persistent Pulmonary Hypertension of the Newborn
Official title: Milrinone Pharmacokinetics and Pharmacodynamics in Newborns With Persistent Pulmonary Hypertension of the Newborn - a Pilot Study to Enable a Randomized Trial of Intervention
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Persistent Fetal Circulation Syndrome
Keywords: Persistent pulmonary hypertension of newborn
PPHN
Persistent pulmonary hypertension
Pulmonary hypertension
Pulmonary hypertension of newborn
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: Bedford Pharmaceuticals
name: American Medical Association
name: Thrasher Research Fund
First posted: 2010-03-18
Enrollment: 12
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Define Plasma Concentration-time Profile of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN) - Clearance (CL, mL/Min)
timeFrame: End of bolus dose, 15 minutes prior to end of infusion (EOI), at four time points after EOI with final sample at 12-15 hours after EOI (timing based on infant's weight)
Secondary outcomes:
measure: Change in Oxygenation Index (OI) From Baseline to up to 24 Hours After Start of Milrinone Infusion
timeFrame: for up to 24 hours after start of infusion
measure: Change in Myocardial Performance Index (MPI) From Baseline to up to 24 Hours After Start of Milrinone Infusion
timeFrame: Up to 24 hours after start of infusion
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Children's Hospital of Michigan/Hutzel Women's Hospital
state: Michigan
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Haresh Kirpalani, MD
role: PRINCIPAL_INVESTIGATOR
References: