Project Summary
Infants born preterm are exposed to an array of morbidities. The most common cardiovascular problem
observed in this population is patent ductus arteriosus (PDA). Following surgical closure of a PDA, infants can
develop Post-Ligation Cardiac Syndrome (PLCS), a serious complication which represents a state of severe
postoperative cardiopulmonary instability. PLCS can be observed in up to 50% of extremely premature infants
after surgical closure of the PDA. Recognition and treatment of PLCS often occurs late and treatment is
variable across hospitals. To date, there have been no randomized controlled clinical trials (RCTs) of
cardiovascular drugs to either prevent or treat PLCS in preterm infants. Given the variance in treatment of
PLCS, the potential use of harmful treatments amid suboptimal evidence or scientifically proven justification for
use, a masked, multicenter randomized trial is essential.
Preliminary data suggest that milrinone, a commonly used cardiovascular medication, reduces the risk of
PLCS in neonates requiring surgical ligation for PDA. The proposed Milrinone for Prevention of Post-ligation
Cardiac Syndrome (MIDAS) trial aims to move preliminary research forward by designing and implementing an
RCT to obtain additional data to determine efficacy of prophylactic milrinone at reducing the incidence of PLCS
and improving neonatal outcomes. We will apply the experience and rigor of the Neonatal Research Network
infrastructure in performing randomized placebo-controlled trials in union with RTI’s leadership in statistical
design and analysis and numerous prior successes in the development and implementation of RCTs. The
specific aims for the MIDAS trial are:
• Specific Aim #1: Determine the efficacy of prophylactic milrinone on decreasing PLCS and mortality
in extremely preterm infants, born at gestational age <27 weeks and 6 days, after PDA closure by
surgical ligation or percutaneous cardiac catheterization.
• Subsidiary Aim: Determine the effects of prophylactic milrinone on 2-year survival and incidence
of adverse neurodevelopmental outcomes in extremely preterm infants treated with PDA
ligation.
With successful execution of these planned experimental aims, the DCC will be able to contribute toward
identification of an evidence-based approach (demonstrative of external validity and reproducibility) for the safe
prevention and treatment of PCLS in preterm infants.
