Pistulli 2014.

Methods	Single centre, randomised controlled trial, conducted in the NICU of the University Hospital for Obstetrics and Gynecology, Koço Gliozheni, Tirana, Albania. Study period: January 2010 to December 2012
Participants	80 preterm infants with a PMA 28 to 32 weeks, BW ≤ 2000 grams, postnatal age 48 to 96 hours, RDS treated with mechanical ventilation with additional oxygen requirements above 30% and PDA documented by ECHO Ibuprofen (oral): 44 infants randomised, 7 infants were excluded because of mortality before complete treatment course and 1 infant was excluded because of pulmonary haemorrhage (total 8 infants). Outcomes reported for 36 infants Ibuprofen (IV): 36 infants randomised, 3 infants were excluded because of gastrointestinal bleed and 1 infant was excluded because only 2 doses of ibuprofen were administered (total 4 infants). Outcomes reported for 32 infants
Interventions	Ibuprofen (oral): 10 mg/kg given via an oro‐gastric tube, flushed with 1 mL of sterile water Ibuprofen (IV): 10 mg/kg given via IV route infused over a 15‐minute period with a syringe pump, and the line was subsequently flushed with saline ECHO was performed again 24 hours after each ibuprofen dose. When the PDA was still haemodynamically significant, as demonstrated by ECHO, and there was no evidence of deterioration in brain ultrasonography, a second dose of ibuprofen 5 mg/kg was administered. A third equivalent dose was given after another 24 hours, if deemed necessary
Outcomes	Failure to close a PDA (after single or 3 doses), need for surgical ligation, oliguria, and mean plasma creatinine on day 3 of treatment
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)	Unclear risk	No information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Ibuprofen was given via an oro‐gastric tube in one group and by IV in the other group, so the mode of drug delivery must have been known to caregivers
Blinding of outcome assessment (detection bias) All outcomes	High risk	It was not stated that ECHOs were performed by a paediatric cardiologist blinded to the groups
Incomplete outcome data (attrition bias) All outcomes	High risk	In the oral ibuprofen group, 7 infants were excluded because of mortality before complete treatment course and 1 infant was excluded because of pulmonary haemorrhage. Outcomes reported for 36 infants in the oral ibuprofen group. In the IV ibuprofen group, 3 infants were excluded because of gastrointestinal bleed and 1 infant was excluded because only 2 doses of ibuprofen were administered. Outcomes reported for 32 infants
Selective reporting (reporting bias)	Unclear risk	Study protocol was not available to us so we could not ascertain if there were deviations from the protocol
Other bias	Unclear risk	Appeared free of other bias