PROJECT SUMMARY/ABSTRACT Patent ductus arteriosus (PDA), the most common cardiovascular condition in preterm infants, is associated with mortality and harmful longer-term outcomes including chronic lung disease (CLD) and brain injury. Although treatment does not benefit all infants with PDA, likely due to spontaneous closure, treatment of some infants with symptomatic PDA is necessary. Medications are often used to close persistent preterm PDA in the initial four weeks postnatal, but fail to close the PDA in 1/3 of infants, in whom an intervention is the only remaining definitive closure option (failed pharmacological management). A treatment dilemma exists in the first postnatal month for the subset of infants with persistent, hemodynamically significant, and clinically symptomatic PDA (HSPDA) after postnatal week one following failed pharmacological management. Invasive, intrathoracic PDA surgery was tra- ditionally employed for infants with HSPDA, but associations between surgery and adverse neurodevelopment prompted widespread adoption of non-interventional, supportive treatment. This watchful-waiting approach avoids or delays procedure-related complications, but prolongs developing brain and lung exposure to PDA- related hemodynamics. Evidence is emerging that duration of HSPDA exposure is an important predictor of CLD and/or death. Percutaneous catheter-based closure (PPC) is a novel, minimally-invasive means of closing a HSPDA. A duct occluder (ADO-II AS) was recently approved (1/2019) by the US FDA for preterm infants weigh- ing ≥700 grams. However, the effectiveness of PPC in improving important neonatal outcomes relative to sup- portive (non-intervention) HSPDA management has never been evaluated via a randomized trial (RCT). The uncertainty is whether PPC should be performed early (days 7-30 postnatal) for all infants with HSDPA to prevent PDA-related complications or only rarely as a last resort following a prolonged trial of supportive management. The objective in this application is to determine if PPC improves cardiopulmonary and neurodevelopmental out- comes via a multicenter RCT comparing the two strategies. Aim 1 will determine the effect of PPC versus sup- portive treatment on ventilator-free days (VFDs) at 30 days post-randomization (non-survivors will be scored as having zero VFDs). Aim 2 will determine the effect of PPC versus supportive treatment on secondary cardiopul- monary, safety and neurodevelopmental outcomes at 4 months corrected age (CA). Aim 3 will evaluate whether neurodevelopment at 3-4 months CA is mediated by improved neurodevelopmental profiles at 34-36 weeks PMA. Aim 4 will evaluate potential effect modifiers of HDPSA (e.g., sex, race/ethnicity, gestational age, age at randomization) on VFDs and secondary outcomes. This trial will immediately advance the care of extremely preterm infants with HSPDA following failed medical management by identifying whether PPC or supportive treatment better improves cardiopu...