Persistent Fetal Circulation SyndromeNCT01088997
Pharmacokinetic Study of Milrinone in Babies With Persistent Pulmonary Hypertension of the Newborn
A study testing Milrinone Lactate in people with Persistent Fetal Circulation Syndrome, run by Children's Hospital of Philadelphia at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages Up to 10 days
- Conditions the study is for
- Persistent Fetal Circulation Syndrome
- What is being tested?
- Milrinone Lactate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2010to May 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 10 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital of Michigan/Hutzel Women's Hospital
Detroit, Michigan, 48201-2196
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
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).
Read the 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.
- Conditions
- Persistent Fetal Circulation Syndrome
- Being tested
- Milrinone Lactate
- Keywords
- Persistent pulmonary hypertension of newborn, PPHN, Persistent pulmonary hypertension, Pulmonary hypertension, Pulmonary hypertension of newborn
- Medical subject headings
- Persistent Fetal Circulation Syndrome, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milrinone LactateDrug
Also called Milrinone
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Milrinone Lactate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Oxygenation Index (mean airway pressure*Fraction of Inspired Oxygen/Partial Pressure of Oxygen in the blood) was calculated at baseline and every 6 hours after start of infusion until 12-24 hours after initiation of milrinone infusion.
Measured: 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
An echocardiogram obtained while on milrinone was obtained with the goal of attempting to look for improvements in parameters associated with pulmonary hypertension. The primary parameter measured was the myocardial performance index (MPI). An Echocardiogram was performed at baseline (pre-infusion) and repeated 12-24 hours ater the initiation of the Milrinone infusion. Also known as the Tei index, the MPI is an index that incorporates both systolic and diastolic time intervals in expressing global systolic and diastolic ventricular function. Systolic dysfunction prolongs preejection (isovolumic contraction time, IVCT) and a shortening of the ejection time (ET). Both systolic and diastolic dysfunction result in abnormality in myocardial relaxation which prolongs the relaxation period (isovolumic relaxation time, IVRT). Normal value for MPI is 0.39+/-0.05 with dilated cardiomyopathy value of MPI at 0.59+/-0.10 (both units on a scale)
Measured: Up to 24 hours after start of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2010 (estimated)
- Study startJun 2010
- Primary completionFeb 2013
- Study completionMay 2015
Why it stopped: Inadequate enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Persistent Fetal Circulation SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Bedford Pharmaceuticals, American Medical Association, Thrasher Research Fund
- Responsible party
- Sponsor
- Investigators
- Haresh Kirpalani, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01088997
- Sponsor's protocol ID
- 09-007384
- Status last verified
- Jun 2016
- First submitted
- 12 Mar 2010
- Last updated
- 12 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01088997
- Acronym / sponsor ID
- 09-007384
- Conditions
- Persistent Fetal Circulation Syndrome
- Keywords
- Persistent pulmonary hypertension of newborn, PPHN, Persistent pulmonary hypertension, Pulmonary hypertension, Pulmonary hypertension of newborn
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate enrollment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Bedford Pharmaceuticals, American Medical Association, Thrasher Research Fund
- Study start
- Jun 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 18 Mar 2010 (estimated)
- Results
- Posted 12 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Dose Milrinone | Experimental | Drug: Milrinone LactateSubjects 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. |
| Low Dose Milrinone | Experimental | Drug: Milrinone LactateSubjects 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. |
Who may qualify
- Ages
- Up to 10 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Milrinone LactateAlso: MilrinoneMilrinone 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. | Drug | High Dose Milrinone, Low Dose Milrinone |
Primary outcome
Define Plasma Concentration-time Profile of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN) - Clearance (CL, mL/Min)
Time frame: 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)
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.
2 secondary outcomes
Change in Oxygenation Index (OI) From Baseline to up to 24 Hours After Start of Milrinone Infusion
Time frame: 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
Time frame: Up to 24 hours after start of infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Persistent Fetal Circulation Syndrome
Recruiting
Effect of Melatonin on Pulmonary Hypertension in Full Term Neonates
Congenital Peumonia, Persistent Pulmonary Hypertension of Newborn
Not yet recruitingObservational study
Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Recruiting
Close Loop Smart Weaning for INO With PPHN
Persistent Pulmonary Hypertension of the Newborn, Inhaled Nitric Oxide
Active, not recruiting
Preductal Oxygen Saturation Target in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure or Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxemic Respiratory Failure
RecruitingObservational study
PTGS1 Genetic Variation and Increased Risk for Persistent Pulmonary Hypertension of the Newborn
Persistent Pulmonary Hypertension of the Newborn
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Haresh Kirpalani, MD principal investigator
Children's Hospital of Philadelphia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Milrinone Lactate in people with Persistent Fetal Circulation Syndrome, run by Children's Hospital of Philadelphia at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define Plasma Concentration-time Profile of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN) - Clearance (CL, mL/Min) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2016.