Erdeve 2012

Methods	Single centre, randomised controlled trial, conducted in Ankara, Turkey. Study period: January 2010 to February 2011
Participants	80 infants with PMA ≤ 28 weeks, BW < 1000 grams, postnatal age 48 to 96 hours and with ECHO‐confirmed significant PDA
Interventions	Ibuprofen (oral): 36 infants Ibuprofen (IV): 34 infants Both at a dose of 10 mg/kg followed by 5 mg/kg at 24 and 48 hours. 4 infants in the oral group and 6 in the IV group were excluded because of mortality before complete treatment course
Outcomes	Primary outcome: PDA closure rate Secondary outcomes: mortality, need for re‐treatment or surgical treatment of the PDA, duration of ventilation, duration of hospital stay, increase in serum bilirubin level after treatment, plasma creatinine after the first course of treatment, rate of ductal reopening, pneumothorax, pulmonary haemorrhage, pulmonary hypertension, BPD (supplemental oxygen at 36 weeks' PMA), IVH (grades I‐IV), NEC, ROP and ROP requiring laser treatment
Notes	4 infants in the oral group and 6 in the IV group were excluded because of mortality before complete treatment course. They were not included in an ITT analysis for the outcome of mortality. We did include these deaths in our analysis of mortality. 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	Sequentially numbered, sealed, opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Ibuprofen was administered either orally or IV, which would have been known to the caregivers
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A paediatric cardiologist was blinded to the treatment group to determine the success of the treatment and the need for a second course via the same route
Incomplete outcome data (attrition bias) All outcomes	High risk	4 infants in the oral group and 6 in the IV group were excluded because of mortality before complete treatment course. They were not included in an ITT analysis for the outcome of mortality. We did include these deaths in our analysis of mortality
Selective reporting (reporting bias)	Low risk	Study protocol was available to us. Trial registration # NCT01261117. There did not seem to have been any deviations from the protocol
Other bias	Low risk	Appeared free of other bias