A Phase 3 interventional study of Milrinone infusion and Placebo infusion in Post-ligation Cardiac Syndrome, sponsored by NICHD Neonatal Research Network. Recruiting at 19 sites in United States. Open to participants aged Up to 3 Months. Per ClinicalTrials.gov, last updated 2026-07-01.
Sponsored by NICHD Neonatal Research Network · Phase 3, Interventional, and Prevention
The goal of this Phase 3, randomized, masked clinical trial is to is to find out whether milrinone, when given to infants after PDA closure, will help the heart work better by supplying oxygen to the lungs and tissues.
The main questions it aims to answer are:
Researchers will compare milrinone to a placebo saline solution to see if it helps the heart work better by supplying oxygen to the lungs and tissues.
After randomization the following will happen in both the control and treatment groups:
NICHD Neonatal Research Network is the lead sponsor of 63 studies on the registry; 5 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
An iv infusion of placebo (0.9% saline) of equivalent volume will be administered. The infusion will be accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes) to ensure blinding is maintained.
Drug: Placebo infusion
An intravenous (iv) infusion of milrinone will be administered at an initial dose of 0.33 mcg/kg/min and accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes).
Drug: Milrinone infusion
An intravenous (iv) infusion of milrinone will be administered at an initial dose of 0.33 mcg/kg/min and accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes).
An iv infusion of placebo (0.9% saline) of equivalent volume will be administered. The infusion will be accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes) to ensure blinding is maintained.
Post-ligation cardiac syndrome (PLCS) or death within 7 days of PDA closure
Composite outcome of post-ligation cardiac syndrome (PLCS) or death within 7 days of PDA closure. Onset within 48 hours but may last up to 7 days.
Time frame: Onset within 48 hours but may last up to 7 days
Systemic hypotension
Either systolic blood pressure below the 3rd percentile for gestational age or mean blood pressure below the postmenstrual age equivalent
Time frame: Onset within 48 hours but may last up to 7 days
Systemic hypertension
Systolic blood pressure above the 97th percentile
Time frame: Onset within 48 hours but may last up to 7 days
Oxygenation failure
An absolute increase of at least 20% in the fraction of inspired oxygen or mean airway pressure compared with the one-hour post-intervention value that persists for a minimum of 1 hour and occurs within 72 hours of PDA closure
Time frame: Onset within 48 hours but may last up to 7 days
Ventilation failure
Need for high frequency oscillatory ventilation when conventional ventilation strategies fail or a 20% rise in amplitude compared with the one-hour post-intervention value that persists for a minimum of 1 hour and occurs within 72 hours of PDA closure
Time frame: Within 72 hours of PDA closure
Vasopressor score
Vasopressor score. Minimum score is zero. Higher score is worse, meaning need for higher level of support. VISmax will be calculated as follows: (VIS=dopamine dose \[μg kg-1 min-1\]+dobutamine \[μg kg-1 min-1\]+100×epinephrine dose \[μg kg-1 min-1\]+50×levosimendan dose \[μg kg-1 min-1\]+10×milrinone dose \[μg kg-1 min-1\]+10 000×vasopressin \[units kg-1 min-1\]+100×norepinephrine dose \[μg kg-1 min-1\]) using the maximum dosing rates of vasoactive and inotropic medications (μg kg-1 min-1 or IU kg-1 min-1)
Time frame: Within 7 days of PDA closure
Use of open-label milrinone or systemic vasodilator after cessation of study drug administration
Number of participants using open-label milrinone or systemic vasodilator after cessation of study drug administration
Time frame: After study drug cessation and within 7 days of PDA closure
Time to successful extubation
Time to successful extubation, which is defined as extubation for at least 7 days
Time frame: 36 weeks postmenstrual age
Post-intervention Moderate-severe bronchopulmonary dysplasia at 36 weeks' gestation
Need for at least 2 liters of high flow nasal cannula at 36 weeks postmenstrual age
Time frame: 36 weeks postmenstrual age
Post-intervention Chronic Pulmonary hypertension
presence of septal flattening (or eccentricity index \> 1.3, right ventricular systolic pressure greater than 40 mmHg, or exclusive right to left atrial level shunt on 36-week echocardiography assessment. The presence of a large atrial septal defect, pulmonary vein stenosis or left ventricular diastolic dysfunction will be recorded.
Time frame: 36 weeks postmenstrual age
Post-intervention Periventricular Leukomalacia (PVL)
Presence of cystic white matter changes on cranial ultrasound
Time frame: 36 weeks postmenstrual age
Post-intervention Necrotizing Enterocolitis
At least Bells stage IIb disease
Time frame: 36 weeks postmenstrual age
Post-intervention Retinopathy of Prematurity (ROP) ≥ stage 3 (according to the international classification)
Post-intervention Retinopathy of Prematurity (ROP) ≥ stage 3 (according to the international classification)
Time frame: 36 weeks postmenstrual age
Weight or head circumference z-score change at 36 weeks
Weight or head circumference z-score change at 36 weeks (decline by two z-scores will be considered growth failure)
Time frame: 36 weeks postmenstrual age
Death between randomization and discharge from NICU
Death between randomization and discharge from NICU
Time frame: Randomization to 120 days' postnatal age, death, discharge, or transfer outside of the Study Center, whichever occurs first (an average of 112 days postnatal age)
Moderate-Severe neurodevelopmental impairment (NDI), using current NRN Follow-Up Study definition
Moderate-Severe neurodevelopmental impairment (NDI), using current NRN Follow-Up Study definition
Time frame: 22 to 26 months
Moderate-Severe neurodevelopmental impairment (NDI) or death
Moderate-Severe neurodevelopmental impairment (NDI) or death
Time frame: 22 to 26 months
Moderate or severe cerebral palsy
Moderate or severe cerebral palsy
Time frame: 22 to 26 months
Severe vision impairment
Severe vision impairment
Time frame: 22 to 26 months
Severe hearing impairment
Severe hearing impairment
Time frame: 22 to 26 months
Bayley-4 cognitive, language, motor scores
Bayley-4 cognitive, language, motor scores
Time frame: 22 to 26 months
Gross Motor Function level ≥II
Gross Motor Function level ≥II
Time frame: 22 to 26 months
CBCL Internalizing, Externalizing, and Total Problems aggregate T scores of >64 (clinical range) and 60-63 (borderline range).
CBCL Internalizing, Externalizing, and Total Problems aggregate T scores of \>64 (clinical range) and 60-63 (borderline range).
Time frame: 22 to 26 months
Death before 22-26-month follow-up
Death before 22-26-month follow-up
Time frame: 22 to 26 months
Height, weight, or head circumference growth failure
Height, weight, or head circumference growth failure (decline by \>2 z-scores since discharge)
Time frame: 22 to 26 months
PDFs hosted by the registry, ClinicalTrials.gov.
Started Jun 2025 (actual). Primary completion is estimated for Jun 2027, 24 months after the start.
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Studies of the drug tested here: Milrinone
NICHD Neonatal Research Network