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

NCT01088997 | Terminated Results DMC

• 1 other identifier: 09-007384
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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).

Conditions

Persistent Fetal Circulation Syndrome

Keywords

Persistent pulmonary hypertension of newborn; PPHN; Persistent pulmonary hypertension; Pulmonary hypertension; Pulmonary hypertension of newborn

Outcome Measures

Primary Outcomes (1)

• Define Plasma Concentration-time Profile of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN) - Clearance (CL, mL/Min)

  The schedule of milrinone pharmacokinetic (PK) sampling varied by weight to minimize blood sampling. For babies weighing less than 3kg, samples were drawn at the end of the bolus, 15 minutes prior to the end of infusion (EOI) and 20 minutes, 1, 2, 6 and 12 hours after EOI. For babies weighing 3kg or more, samples were drawn at the end of the bolus, 6 hours after start of infusion, 15 minutes prior to the EOI and 30 minutes, 1, 3, 9 and 15 hours after EOI. Milrinone plasma concentrations were determined using a validated high-performance mass spectrometry assay.

  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 (2)

• Change in Oxygenation Index (OI) From Baseline to up to 24 Hours After Start of Milrinone Infusion

  for up to 24 hours after start of infusion

• Change in Myocardial Performance Index (MPI) From Baseline to up to 24 Hours After Start of Milrinone Infusion

  Up to 24 hours after start of infusion

Study Arms (2)

High Dose Milrinone

EXPERIMENTAL

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.

Drug: Milrinone Lactate

Low Dose Milrinone

EXPERIMENTAL

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.

Drug: Milrinone Lactate

Interventions

Milrinone Lactate DRUG

Milrinone lactate will be given first as an IV bolus over one hour at the assigned dose level, followed by a 24 hour IV infusion at the assigned dose level.

Also known as: Milrinone

High Dose Milrinone; Low Dose Milrinone

Eligibility Criteria

• Age: Up to 10 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• University of Pennsylvania: collaborator
• Bedford Pharmaceuticals: collaborator
• American Medical Association: collaborator
• Thrasher Research Fund: collaborator

Study Sites (2)

Children's Hospital of Michigan/Hutzel Women's Hospital

Detroit, Michigan, 48201-2196, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Persistent Fetal Circulation Syndrome; Hypertension, Pulmonary

Interventions

Milrinone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study enrollment was terminated early resulting in a small number of evaluable subjects for analysis.

Results Point of Contact

• Title: Haresh Kirpalani, MD, MSc
• Organization: Children's Hospital of Philadelphia

kirpalanih@email.chop.edu

215-590-2455

Study Officials

• Haresh Kirpalani, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 18, 2010
• Study Start: June 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: May 1, 2015
• Last Updated: July 12, 2016
• Results First Posted: July 12, 2016

Record last verified: 2016-06

Locations

US (2)