Yang 2016

Methods	Randomised controlled trial conducted at the Neonatal Ward of the Affiliated Xuzhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu, China Study period from October 2012 to June 2015
Participants	Preterm infants with PMA < 37 weeks and admitted to hospital within 24 h after birth. A significant PDA diagnosis was made between 15 h to 10 days after birth and confirmed through ECHO to be a significant PDA. Diagnostic criteria of echocardiography were: i) left atrial: aortic root diameter ratio, (LA:Ao) > 1.4; ii) pulmonary artery diastolic back flow (reflux); and iii) PDA vessel diameter > 1.4 mm
Interventions	The paracetamol group (n = 44) received 15 mg/kg acetaminophen administered orally once every 6 h for 3 days The ibuprofen group (n = 43) received 10 mg/kg ibuprofen administered orally as the initial dose, followed by 5 mg/kg during the first 24 h and 48 h later
Outcomes	Primary outcome: failure of primary ductal closure Secondary outcomes: oliguria (< 1 mL/kg/h, stools positive for occult blood, IVH (grade not stated), NEC, BPD (PMA not stated), plasma PGE₂ (ng/L), urine PGE₂ (ng/L), platelet count (x10⁹/L), serum Cr (µmol/L), glutamic‐pyruvic transaminase (U/L)
Notes	Patients were excluded from the study if: i) patients presented with any of the following medication contraindications such as thrombocytopenia (blood platelet count < 50 × 10⁹/L), haemorrhagic disease, oliguria (urine volume per 8 h < 8 mL/kg), necrotizing colitis, intestinal perforation, high serum creatinine (> 159.1 μmol/L), and alanine aminotransferase (> 40 U/L) levels; ii) patients had congenital heart diseases such as ventricular septal defect, complex heart disease; iii) patients had incomplete treatment or wished to depart from the study due to personal reasons.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated random number table was used
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	The dosing/timing schedule differed between the 2 drugs, so staff must have known which drug was given
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	It is not stated that the ECHOs were performed by a person blind to the treatment groups
Incomplete outcome data (attrition bias) All outcomes	Low risk	All outcomes reported for all randomised infants
Selective reporting (reporting bias)	Unclear risk	The authors do not indicate that the study was registered in a trials registry at the protocol stage so we cannot judge if there were any deviations from the protocol or not
Other bias	Low risk	Appears free of other bias