Selective early medical treatment of the patent ductus arteriosus in extremely low gestational age infants: a pilot randomised controlled trial (SMART-PDA)

Objectives To assess feasibility of recruitment and compare clinical outcomes in a trial of early selective treatment of a moderate–severe patent ductus arteriosus (PDA) or no intervention in the first 7 postnatal days in extremely preterm infants. Design Multicentre, open-label, parallel-design pilot randomised controlled trial Setting Seven tertiary/quaternary neonatal intensive care units. Patients Infants <26 weeks gestational age (GA) with a PDA diagnosed within 72 hours after birth. Interventions Participants were randomised to an early echocardiographic screening within the first 72 hours followed by selective medical treatment (SMART) strategy of a moderate–severe PDA shunt or no intervention in the first 7 days. Main outcome measures The primary feasibility outcome was the proportion of eligible infants enrolled. Important secondary outcomes included a composite clinical endpoint of survival without major morbidity. Results 116 of 185 eligible infants were enrolled (63%, 95% CI 56% to 70%; SMART, n=51, Control, n=53). Of them, 104/116 (90%) (mean GA 24.3 weeks, birth weight 714 g) were randomised. Protocol deviation was 1.9%. Based on the treatment algorithm, 24% infants randomised to SMART never required treatment. Median treatment initiation age in the SMART arm was 2 days (IQR 1–2.5 days). The SMART strategy demonstrated an 85% probability of a better Win ratio (1.34, 95% CrIs 0.73 to 2.5) compared with control. Conclusions A trial of selective early PDA pharmacotherapy based on clinical and echocardiography grading of PDA shunt volume in the smallest infants is feasible with minimal protocol deviation. Early echocardiography screening and selective pharmacotherapy using the SMART-PDA algorithm may enhance the probability of survival with less morbidities in infants born <26 weeks GA. Trial registration number NCT05011149 .