El‐Mashad 2017.

Methods	Randomised controlled trial in the NICU of Tanta University Hospital, Pediatric department, Tanta University Hospital, Tanta, Egypt. Study period: January 2012 to December 2015
Participants	Preterm neonates with PMA < 28 weeks or birth weight < 1500 grams in the first 2 weeks of life with haemodynamically significant PDA (hs‐PDA) diagnosed with ECHO and clinical examination
Interventions	Experimental intervention: Group I (paracetamol group): 100 neonates received 15 mg/kg IV infusion paracetamol over 30 min followed by 15 mg/kg/6 H IV infusion for 3 days. Group II (Ibuprofen group): 100 neonates received 10mg/kg IV infusion ibuprofen followed by 5 mg/kg/day for 2 days Group III (Indomethacin group): 100 neonates received 0.2 mg/kg indomethacin IV infusion over 30 min for three doses 12 H apart
Outcomes	Primary: Failure to close the PDA Secondary: Surgical ligation, ROP, GI bleeding, NEC, pulmonary haemorrhage, IVH, sepsis, daily urine output, serum creatinine, serum bilirubin, and platelet count
Notes	This was a three arm trial comparing paracetamol to ibuprofen and indomethacin. For this review, we compared the results in the ibuprofen group to the indomethacin group. Funding: "None to declare"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random allocation software was used for random sequence generation
Allocation concealment (selection bias)	Low risk	Sequentially numbered sealed opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	The neonates were enrolled into the respective group by the doctor on duty, who was not blinded and not part of the study. Drugs were given at different times and duration
Blinding of outcome assessment (detection bias) All outcomes	Low risk	ECHOs were performed by a paediatric cardiologist, who was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes reported on all randomised infants
Selective reporting (reporting bias)	Unclear risk	The study was not registered in a trials registry so we could not tell if there were any deviations from the protocol
Other bias	Low risk	Appeared free of other bias