# 1/2 Milrinone for Prevention of Post-Patent Ductus Arteriosus Closure Syndrome in Extremely Preterm Infants (MIDAS Trial) – CCC

> **NIH NIH UG3** · UNIVERSITY OF IOWA · 2024 · $342,731

## Abstract

PROJECT SUMMARY
Significance: Prematurity a major health problem in the United States, with more than 385,000 babies born
preterm annually. The economic cost is more than $50 billion, mostly in extremely low birth weight infants
(ELBW, born<1000g). Patent ductus arteriosus (PDA) is the most common cardiovascular problem and
requires interventional closure in 16% of cases. Intervention is complicated by Post-Ligation Cardiac Syndrome
(PLCS), characterized by low or high blood pressure and respiratory instability, with highest incidence in the
most immature patients. Both PDA surgery and PLCS are independently associated with increased risk of
adverse respiratory outcomes and neuro-developmental disabilities. Of surviving ELBW infants after PDA
closure, 50% had neurodevelopmental impairment including severe handicaps. Postprocedural instability is
decreased by early milrinone use, a vasodilator drug which enhances heart function. Avoiding postprocedural
instability and establishing the safety of milrinone are considered important outcomes by parents.
Investigators and Prior Work: Prospective observational mechanistic data demonstrates that PLCS relates to
inability of the immature myocardium to tolerate the change in left ventricular loading conditions. Preliminary
data demonstrates the efficacy of milrinone in reducing the incidence of PLCS through optimizing heart
function. The Clinical Coordinating Center MPI Dr. Patrick McNamara, a world leading hemodynamics
scientist, conducted the original mechanistic studies which characterized the biological mechanisms of PLCS
and the pharmacology of milrinone. Dr Edward Bell (MPI) has an extensive record in leading multicenter
clinical trials and the Data Coordinating Center (DCC) PI Dr. Abhik Das has led several NHLBI funded trials.
Innovation: In most centers PLCS is recognized late, when hypotension is severe, and prompts use of
vasopressor drugs which impair heart function. There are no prior randomized clinical trials of milrinone after
PDA closure; therefore, neither treatment efficacy nor long-term safety is known. We propose a randomized
controlled trial (RCT) to evaluate the immediate benefits of milrinone in decreasing the rate of PLCS and 7-day
mortality. The need to assess long-term outcomes of RCTs is compelling to ensure treatment safety.
Approach: We will perform a RCT in preterm infants born less than 28 weeks’ gestation asking: “Does routine
use of intravenous milrinone lower the risk of PLCS or mortality within 7 days of intervention and is treatment
safe?” The question is relevant to the mission of NHLBI and aligns with parental values to minimize
postprocedural risk. In addition, it represents a paradigm shift in Neonatology to conduct clinical trials of
treatments that offer biologic plausibility in illnesses that have been mechanistically characterized.
Environment: We have partnered with the NICHD Neonatal Research Network (NRN), which includes 15
clinical centers, and have added 4 a...

## Key facts

- **NIH application ID:** 10806032
- **Project number:** 1UG3HL166579-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** EDWARD F BELL
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $342,731
- **Award type:** 1
- **Project period:** 2024-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806032

## Citation

> US National Institutes of Health, RePORTER application 10806032, 1/2 Milrinone for Prevention of Post-Patent Ductus Arteriosus Closure Syndrome in Extremely Preterm Infants (MIDAS Trial) – CCC (1UG3HL166579-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10806032. Licensed CC0.

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