Al‐Lawama 2017

Methods	Randomised controlled study conducted in the Neonatal Intensive Care Unit of Jordan University Hospital, Amman, Jordan. Study period: from March 2015 to October 2016
Participants	Inclusion criteria: preterm infants with a gestational age of ≤ 32 weeks or birth weight of ≤ 1500 g and a haemodynamically significant PDA diagnosed by ECHO. Exclusion criteria: ductal‐dependent congenital heart diseases, major congenital malformation, grade 3 to 4 intraventricular haemorrhage, renal impairment (defined as a creatinine concentration of > 1.5 mg/dL), pulmonary haemorrhage, thrombocytopenia of < 60,000/mm³ , and an elevated alanine transaminase concentration
Interventions	The oral paracetamol group (n = 13) received 10 mg/kg/dose followed by 1 to 2 mL of 0.9% saline every 6 h for 3 days. (10 mg/kg every 6 h for 3 days). The oral ibuprofen group (n = 9) received 10 mg/kg/dose followed by 1 to 2 mL of 0.9% saline once daily for 3 days. (10 mg/kg/day for 3 days). The researchers used the same dose for the 3‐day course to minimize errors
Outcomes	Primary outcome: mortality, primary PDA closure. Secondary outcomes: secondary PDA closure, pulmonary haemorrhage, BPD, Sepsis, NEC, ROP, IVH Grade 1 to 2, IVH Grade 3 to 4, PVL
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised by computer to receive either oral paracetamol or oral ibuprofen
Allocation concealment (selection bias)	Low risk	Randomisation numbers were placed inside sequentially numbered opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	There were different scheduling regimens for paracetamol and ibuprofen, so staff were not blinded to the drugs administered
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	It is not stated whether the person conducting ECHO cardiography was blinded to the treatment or not
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised infants are accounted for
Selective reporting (reporting bias)	Unclear risk	The study was registered: ISRCTN12302923 DOI 10.1186. The study was registered in retrospect when it was completed, so we cannot judge if there were any deviations from the original protocol
Other bias	Low risk	Appears free of other bias