Milrinone for Prevention of Post-ligation Cardiac Syndrome Trial

NCT06679855 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: NICHD-NRN-0066
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 19

Brief Summary

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:

1. 1.to determine if milrinone decreases the risk of death or PLCS within 7 days of the procedure, compared to standard treatment; and
2. 2.to determine the effects of milrinone on two-year survival and neurodevelopmental outcome.

Conditions

Post-ligation Cardiac Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  Onset within 48 hours but may last up to 7 days

Secondary Outcomes (24)

• Systemic hypotension

  Onset within 48 hours but may last up to 7 days

• Systemic hypertension

  Onset within 48 hours but may last up to 7 days

• Oxygenation failure

  Onset within 48 hours but may last up to 7 days

• Ventilation failure

  Within 72 hours of PDA closure

• Vasopressor score

  Within 7 days of PDA closure

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Milrinone

ACTIVE COMPARATOR

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

Interventions

Milrinone infusion DRUG

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).

Milrinone

Placebo infusion DRUG

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.

Placebo

Eligibility Criteria

• Age: Up to 3 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age at birth ≤27 weeks (and 6 days) and postnatal age \< 3 months at intervention
• Invasive or non-invasive positive pressure respiratory support (does not include low flow nasal cannula)
• Hemodynamically significant PDA with minimum transductal diameter ≥1.0 mm within 2 days of intervention
• Decision by clinical team to proceed with PDA closure via surgical ligation or percutaneous cardiac catheterization based on clinical and echocardiography features of hemodynamic significance.

You may not qualify if:

• Any major congenital malformation
• Congenital heart disease (except small (≤1mm) muscular ventricular septal defects, or small/moderate (\<3mm) atrial septal defect)
• Acute renal failure defined by urine output \< 0.5 mL/kg/hour OR rise of serum creatinine by 0.3 mg/dL within 48 hours OR rise of serum creatinine more than 40% above baseline serum creatinine within prior 72 hours.
• Systemic administration of vasodilator/inodilator agents
• Prior history of arrhythmia

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (19)

University of Alabama - Birmingham

Birmingham, Alabama, 35249, United States

NOT YET RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

NOT YET RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

NOT YET RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Northwestern Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

NOT YET RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87131, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Case Western Reserve University

Cleveland, Ohio, 44106, United States

RECRUITING

University of Oklahoma Health Sciences

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

University of Texas at Houston

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84108, United States

RECRUITING

Related Publications (1)

• McNamara PJ, Chock VY, Rahde-Bischoff A, Gabrio J, Johnson KJ, Harmon HM, Montoya-Williams D, Colaizy TT, Katheria AC, Ines F, Sorrells K, Battersby C, Levy PT, Rysavy MA, Bhombal S, Laughon MM, Carper B, Hintz SR, Das A, Bell EF. Evaluating the efficacy and safety of milrinone for prevention of post-patent ductus arteriosus closure syndrome (the MIDAS trial) in extremely preterm infants: a multicentre, double-masked, randomised, placebo-controlled trial. BMJ Open. 2025 Aug 26;15(8):e105018. doi: 10.1136/bmjopen-2025-105018.

  PMID: 40858367 DERIVED

Central Study Contacts

Patrick J McNamara

CONTACT

319-467-7435; patrick-mcnamara@uiowa.edu

Valerie Chock

CONTACT

650-723-5711; vchock@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 8, 2024
• Study Start: June 13, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (19)