Bravo 2014.

Methods	Single centre, randomised placebo‐controlled, double‐blind trial conducted in Madrid, Spain. Study period: 11 months
Participants	49 preterm infants with ECHO‐confirmed PDA measuring ≥ 1.5 mm (PMA 24 to 34 weeks)
Interventions	Infants with PDA ≥ 1.5 mm received the first dose of ibuprofen (10 mg/kg) and were then randomised to receive either standard treatment (21 infants) or ECHO‐guided treatment (28 infants) Standard treatment: 2 additional doses of ibuprofen 5 mg/kg at 24‐hour intervals after the initial dose of 10 mg/kg, independently of ductal size, as long as additional doses were not contraindicated ECHO: additional doses of ibuprofen (5 mg/kg at 24‐hour intervals) only if the PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose. A decision on whether to treat the PDA when the diameter was < 1.5 mm in the ECHO group was made on the basis of previous reports using the same approach with indomethacin. Additional ibuprofen doses were administered only when the PDA was > 1.5 mm 24 hours after a complete ibuprofen course (therapeutic failure), or when a reopening was documented because a diameter ≥ 1.5 mm has been correlated with pulmonary overflow, as small, nonsymptomatic PDA do not seem to play an important role in the pathogenesis of PDA‐related morbidity
Outcomes	Primary outcome: reopening of PDA Secondary outcomes: failure to close a PDA, number of ibuprofen doses used, need for surgical ligation, mortality, BPD (need for supplemental oxygen at 36 weeks' PMA), IVH (grade II and III), PVL, oliguria (urine output < 1 mL/kg/hour), creatinine after treatment and laser therapy for ROP
Notes	Dr. Bravo provided additional information regarding the methods and the outcomes of the trial. The study received financial support from the Spanish Fondo de Investigacion Sanitaria, grant CM07/00111, and the scientific advice of the SAMID network (RD08/0072/0018)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random sequence
Allocation concealment (selection bias)	Low risk	Sequentially numbered opaque envelopes that contained the allocation written on a card inside
Blinding of participants and personnel (performance bias) All outcomes	High risk	Healthcare providers were not blinded to the intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	ECHOs were conducted by the same examiner, who was blind to the patient group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcome data provided for all randomised infants
Selective reporting (reporting bias)	Unclear risk	Study protocol was not available to us so we could not judge if there were any deviations from the protocol
Other bias	Low risk	Appeared free of other bias