Gokmen 2011

Methods	Single centre, randomised, controlled trial conducted at Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey. Study period: January 2010 to February 2011
Participants	108 VLBW infants with PDA
Interventions	Ibuprofen (IV): 54 infants, IV ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours Ibuprofen (oral): 54 infants, oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours 6 infants (4 in the IV group and 2 in the oral group) died before they completed the treatment and were excluded from the analyses
Outcomes	Renal tolerance, mean plasma creatinine after treatment, urine output after treatment, cystatin‐C levels, failure to close a PDA, need for second course of ibuprofen, oliguria, hospital stay, NEC, gastrointestinal bleed, sepsis, pneumothorax, BPD (supplemental oxygen at 36 weeks' PMA or at discharge, which ever came first, ROP requiring laser treatment, and mortality during hospital stay
Notes	In 2013, a follow‐up study of this trial was published. 57 children (56%) of the original 102 infants enrolled in this study were followed to an age of 18 to 24 months corrected age; 30 infants in the oral ibuprofen group and 27 infants in the IV ibuprofen group were assessed for long‐term outcomes. The following outcomes were reported; Mental (MDI) and Psychomotor (PDI) Developmental Index on Bayley Scales of Infant Development II, moderate/severe cerebral palsy with functional deficits that required rehabilitation services, bilateral hearing loss (requiring amplification), blindness in either eye, MDI < 70 and PDI < 70. Information on funding was not 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	Infants were assigned randomly using cards in sealed, opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Ibuprofen was given either orally or IV and this would have been known to staff
Blinding of outcome assessment (detection bias) All outcomes	Low risk	ECHOs were performed by a paediatric cardiologist, who was blinded to the treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	6 infants (4 in the IV ibuprofen group and 2 in the oral group) died before they completed their treatment. These infants were not included in an ITT analysis. We included them in our analyses
Selective reporting (reporting bias)	Unclear risk	The protocol for this study was not available to us and we could not ascertain whether there were deviations from the protocol
Other bias	Low risk	Appeared free of other bias