Persistent Pulmonary Hypertension of Newborn (PPHN) Clinical Trial
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
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).
| Status | Terminated |
| Enrollment | 10 |
| Est. completion date | May 2015 |
| Est. primary completion date | February 2013 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | N/A to 10 Days |
| Eligibility |
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 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 ECMO or plan to initiate ECMO within 2 hours of enrollment |
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Children's Hospital of Michigan/Hutzel Women's Hospital | Detroit | Michigan |
| United States | The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Haresh Kirpalani | American Medical Association, Bedford Pharmaceuticals, Thrasher Research Fund, University of Pennsylvania |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Pharmacokinetic profile of milrinone in newborns with PPHN | For infants <3 kg, samples will be collected at end of bolus, 15min prior to end of infusion (EOI), and after EOI at 20min, 1hr, 2hr, 6hr, & 12 hr. For infants >3 kg, samples will be collected at end of bolus, 6 hours after start of infusion, 15min prior to end of infusion (EOI), and after EOI at 30min, 1hr, 3hr, 9hr, & 15 hr. Samples will be stored at -70C and milrinone plasma concentrations measured by modification of a high-pressure liquid chromatography assay in laboratory of Clinical Pharmacology and Therapeutics at CHOP. | according to weight (see below) | No |
| Secondary | Oxygenation index | Oxygenation index (mean airway pressure*FiO2/PaO2) will be calculated every 6 hours. | every 6 hours for 48 hours | No |
| Secondary | Echocardiographic signs of pulmonary hypertension | An echocardiogram obtained while on milrinone will look for improvements in parameters associated with 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. | 12-24 hours | No |
| Secondary | Safety profile | Safety analysis will be performed as follows: blood pressure will be monitored hourly for 48 hours, platelet count will be recorded daily, cardiac rhythm will be monitored continuously for 48 hours, renal function will be recorded daily, and liver transaminases will be recorded within a week. All adverse events will be included in the safety analysis. Interim safety analyses will be performed after 1/3 and 2/3 of subjects have been enrolled. A data safety monitoring committee will meet monthly to discuss adverse events and interim analyses. | 24-48 hours | Yes |