Lin 2017

Methods	Randomised controlled trial conducted in two NICUs in John Stroge's Hospital of Cook County, Chicago, USA and in Chaina Medical University Hospital, Taiwan. Study period: not stated
Participants	Inclusion criteria: : (1) preterm infants with a birth weight < 1,000 g; (2) a radiographic figure of respiratory distress syndrome; (3) requirement for mechanical ventilation, and (4) echocardiography proven and clinically significant PDA
Interventions	Infants assigned to ibuprofen were given an initial dose of 10 mg/kg (1.0 mL/kg) followed by 2 doses of 5 mg/kg (0.5 mL/kg) at 24‐hour intervals IV Infants assigned to the indomethacin group were given an initial dose of 0.2 mg/kg (1.0 mL/kg) followed by 2 doses of 0.1 mg/kg (0.5 mL/kg) at 24‐hour intervals IV
Outcomes	Primary outcomes – renal function and ductal response; reopening, persistent ductal closure, and surgical ligation. NEC, BPD (age not stated), IVH (≥ grade 2)
Notes	The study was funded by Lundbeck (Ovation) Pharmaceuticals (Chicago, Ill, USA) and the National Science Council (NSC 95‐2314‐B‐039‐032‐MY2), Taipei, Taiwan
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated
Allocation concealment (selection bias)	Low risk	Sealed envelopes
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Both medications were clear and indistinguishable, and for each administration a similar volume was infused continuously over a period of 15 min. During the study, only the primary investigator in each participating hospital was aware of the content of the medication, while the other medical and nursing staff responsible for daily care were blinded to the medication administered. The primary investigator was either the chief or the consultant of the NICU, who was rarely involved in direct patient care
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The ECHOs were read by a paediatric cardiologist who was blinded to the study medication
Incomplete outcome data (attrition bias) All outcomes	High risk	Outcome group; before the data were analysed, two infants with a birthweight of < 500 g and four infants with intractable respiratory failure and with severe IVH were excluded – thus not intention‐to‐treat analysis. These infants fulfilled inclusion criteria
Selective reporting (reporting bias)	Unclear risk	The trial was registered as NCT01758913, but only in 2013. The study took place between 2007 and 2012 and therefore the study was completed before it was registered. Thus we cannot ascertain whether there were any deviations from the original protocol.
Other bias	Low risk	Appeared free of other bias