Gournay 2004.

Study characteristics
Methods	Multi‐center (11 centres) randomized controlled trial
Participants	Inclusion criteria Gestational age < 28 weeks, postnatal age less than 6 hours, signed parental consent. Exclusion criteria Major congenital malformations Proven severe congenital maternal‐fetal infection Hydrops fetalis IVH grade 3 to 4 Clinical bleeding Shock or right‐to‐left ductal shunt evidenced by differential cyanosis (pre‐post SpO2 difference>5%) Cerebral complications (convulsions; coma) Bleeding disorders
Interventions	Active intervention (n = 65) Prophylactic IV ibuprofen lysine; loading dose 10 mg/kg followed by 2 maintenance doses of 5 mg/kg at 24‐hour intervals (equivalent volumes for placebo), each infused over 20 minutes Control (n = 66) Blinded IV placebo (2 mL vials with 0.9% saline)
Outcomes	Relevant outcomes for this study included Mortality IVH CLD (oxygen supplementation beyond 28 days) NEC Gastrointestinal perforation Treatment for symptomatic PDA Surgical PDA ligation Periventricular leukomalacia Oliguria
Notes	Primary study location: the primary study location was Nantes, France. The study was conducted across 11 tertiary neonatal care units across France Study period: March 2001 to December 2001 Trial registration: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Sequence generation method not specified.
Allocation concealment (selection bias)	Low risk	Sealed envelope allocation kept at hospital pharmacy.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo (0.9% saline) was used suggesting that personnel were blinded to the allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Placebo (0.9% saline) was used suggesting that outcome assessors were blinded to the allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	135 infants were included in the study; 4 infants were not randomized due to errors in study drug allocation (3 mistakenly received open‐label ibuprofen during their prophylactic course, and one 10‐day‐old with diagnosis of PDA was mistakenly given 2 doses of placebo instead of open‐label therapeutic ibuprofen. Per‐protocol analyses were performed on 131 infants. No participants were lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	The trial was not pre‐registered in any trials registry
Other bias	Unclear risk	The study was sponsored by the manufacturers of the intervention drug ibuprofen lysine (Orphan Europe, Paris, France). The sponsors were involved in the study design, data management, data analysis and data interpretation. All final data analyses were double checked by one of the co‐authors (JCR) who had free access to the raw data.