Aranda 2009.

Methods	Multicentre, randomised controlled trial conducted in 11 centres in the USA. Study period: March 2002 to March 2005
Participants	136 preterm infants (BW 500 to 1000 grams; PMA < 30 weeks) with evidence of ductal shunting by ECHO Mean (SD) GA 26.2 (1.4) weeks, BW 798 (130.3) grams, 51% boys, 49% girls
Interventions	Ibuprofen: 68 infants, IV as 3‐day treatment course of 10 mg/kg, 5 mg/kg and 5 mg/kg Placebo: 68 infants, saline
Outcomes	Proportion of infants who required rescue treatment for PDA (indomethacin or surgery), died or dropped out on or prior to study day 14, mortality, NEC, IVH, pulmonary haemorrhage, pulmonary hypertension, ROP, BPD (supplemental oxygen at 28 days), BPD (supplemental oxygen at 36 weeks' PMA), PVL
Notes	This study was published in abstract form in 2005, but was published in a complete report in 2009. This study was supported by National Institues of Health grant 5‐U01HD‐37261‐01. Funding and Study Sponsor: Ross Laboratories, Columbus, Ohio in collaboration with the NICHD Pediatric Pharmacology Research Unit Network
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomisation was implemented using a dynamic allocation method of biased coin randomisation, balancing within BW (500 to 750 grams and 751 to 1000 grams), within each site, and in the study overall
Allocation concealment (selection bias)	Low risk	The coded vials of study drug or placebo contained indistinguishable colourless solutions dispensed by the blinded research pharmacists of the participating sites
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The coded vials of study drug or placebo contained indistinguishable colourless solutions dispensed by the blinded research pharmacists of the participating sites
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The coded vials of study drug or placebo contained indistinguishable colourless solutions dispensed by the blinded research pharmacists of the participating sites. Outcome assessors were blinded to the group assignments
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The outcome of BPD (supplemental oxygen at 36 weeks' PMA) was not ascertained in the whole sample as randomised. The denominator in the ibuprofen group was 46 infants and in the placebo group it was 52, which is too low when accounting for mortality
Selective reporting (reporting bias)	Unclear risk	See incomplete data. The trials was registered with clinicaltrials.gov: ID # NCT00440804
Other bias	Low risk	Appeared free of other bias