Dani 2012

Methods	Multicentre, randomised, controlled trial conducted in four NICUs (Florence, Turin, Bozen, Milan) in Italy: Study period July 2007 to June 2009
Participants	70 infants with PMA < 29 weeks, ECHO evidence of significant PDA, aged 12 to 24 hours and RDS necessitating respiratory support
Interventions	High‐dose ibuprofen: 35 infants, mean (SD) PMA 25.6 (1.8) weeks; BW 781 (225) grams) randomised to high‐dose ibuprofen 20‐10‐10 mg/kg/day Standard‐dose ibuprofen: 35 infants, mean (SD) PMA 26.0 (1.7) weeks; BW 835 (215) grams) randomised to standard‐dose IV ibuprofen 10‐5‐5 mg/kg/day
Outcomes	Ductal closure, serum creatinine on day 3 of treatment, oliguria (≤ 1 mL/kg/hour during a 24‐hour collection period), peak total serum bilirubin during the first week of life, IVH (all grades and grades III‐IV), PVL (all grades), ROP (all stages, stage > 2), NEC, BPD (oxygen requirement at 36 weeks' PMA), sepsis, mortality and hospital stay (days)
Notes	No information on funding provided
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	It was not stated if clinical staff members were blinded to the dose of ibuprofen the infant received
Blinding of outcome assessment (detection bias) All outcomes	Low risk	ECHO studies were performed by physicians, who were blinded as to the infants' treatment assignments
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes reported for all enrolled infants
Selective reporting (reporting bias)	Low risk	The trial was registered with ClinicalTrials.gov under identifier NCT01243996. There did not seem to have been any deviations from the published protocol
Other bias	Low risk	Appeared free of other bias