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

This study has been terminated.
(Inadequate enrollment)
Sponsor:
Collaborators:
University of Pennsylvania
Bedford Pharmaceuticals
American Medical Association
Thrasher Research Fund
Information provided by (Responsible Party):
Haresh Kirpalani, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01088997
First received: March 12, 2010
Last updated: May 29, 2014
Last verified: May 2014

March 12, 2010
May 29, 2014
June 2010
February 2013   (final data collection date for primary outcome measure)
Pharmacokinetic profile of milrinone in newborns with PPHN [ Time Frame: according to weight (see below) ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01088997 on ClinicalTrials.gov Archive Site
  • Oxygenation index [ Time Frame: every 6 hours for 48 hours ] [ Designated as safety issue: No ]
    Oxygenation index (mean airway pressure*FiO2/PaO2) will be calculated every 6 hours.
  • Echocardiographic signs of pulmonary hypertension [ Time Frame: 12-24 hours ] [ Designated as safety issue: No ]
    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.
  • Safety profile [ Time Frame: 24-48 hours ] [ Designated as safety issue: Yes ]
    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.
  • Oxygenation index [ Time Frame: every 6 hours for 48 hours ] [ Designated as safety issue: No ]
    Oxygenation index (mean airway pressure*FiO2/PaO2) will be calculated every 6 hours.
  • Echocardiographic signs of pulmonary hypertension [ Time Frame: 12-24 hours ] [ Designated as safety issue: No ]
    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.
  • Safety profile [ Time Frame: 24-48 hours ] [ Designated as safety issue: Yes ]
    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. 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.
Not Provided
Not Provided
 
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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Persistent Pulmonary Hypertension of Newborn (PPHN)
Drug: milrinone lactate
Milrinone lactate will be given as an IV infusion for 24 hours.
Other Name: Milrinone lactate
  • Experimental: high dose
    50 mcg/kg load followed by 0.5 mcg/kg/min infusion
    Intervention: Drug: milrinone lactate
  • Experimental: low dose
    20 mcg/kg load followed by 0.2 mcg/kg/min infusion
    Intervention: Drug: milrinone lactate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
10
May 2015
February 2013   (final data collection date for primary outcome measure)

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
Both
up to 10 Days
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01088997
09-007384
Yes
Haresh Kirpalani, Children's Hospital of Philadelphia
Haresh Kirpalani
  • University of Pennsylvania
  • Bedford Pharmaceuticals
  • American Medical Association
  • Thrasher Research Fund
Principal Investigator: Haresh Kirpalani, MD Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP