Management of the PDA Trial (PDA)

Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.

This is a pragmatic randomized multicenter, effectiveness study comparing active treatment of a symptomatic patent ductus arteriosus (sPDA) to expectant management. We hypothesize in premature infants with a sPDA, expectant management reduces the incidence proportion of death or BPD by 10% (from 50% to 40%) when compared to active treatment. Participants with a sPDA allocated to the active treatment arm will receive intravenous administration of indomethacin or ibuprofen (depending on center preference). The decision to ligate will be left to the clinical team. Participants with a sPDA allocated to the expectant management arm will receive supportive care at the clinical team's discretion and will receive indomethacin/ibuprofen or ligation if the infant develops cardiopulmonary compromise. The decision to ligate will be left to the clinical team. The primary endpoint for the study will be death or BPD (as assessed by the physiologic definition) at 36 weeks postmenstrual age (PMA).

Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases, Patent Ductus Arteriosus After Premature Birth

Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other.

Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. If the infant receives both, it will be considered a protocol violation.

Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug

Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug

Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.

Inclusion Criteria: Postnatal age 48 hours -21 days Infant 22 0/7 to 28 6/7 weeks gestation at birth sPDA, as defined as: Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram Mild or Moderate Clinical Criteria with Large PDA on echocardiogram Exclusion Criteria: Cardiopulmonary compromise Known congenital heart disease (besides atrial septal defect or ventricular septal defect) Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary adenomatous malformation) Any condition which, in the opinion of the investigator, would preclude enrollment