Sanghvi 2017.

Methods	2‐centre randomised, placebo‐controlled trial performed in Mumbai, India. Allocation concealment: yes. Randomisation: computer‐based random number generation (blocks of 2 or 4). Blinding of caregivers and personnel to intervention: yes. Blinding of outcome ascertainment: yes (ophthalmologists). Complete follow‐up: yes.
Participants	Preterm neonates (n = 109 enrolled, n = 102 analysed). Inclusion criteria: gestational age 26 to 32 weeks, postnatal age < 8 days. Participants were stratified into 2 groups according to gestational age (26 to 28 weeks' gestational age, 29 to 32 weeks' gestational age). Intervention group: mean (SD) gestational age 29.54 (± 1.69) weeks; mean (SD) postnatal age 5.78 (± 1.74) days; mean (SD) birth weight 1235 grams (± 280). Control group: mean (SD) gestational age 29.12 (± 1.74) weeks; mean (SD) postnatal age 5.96 (± 1.87) days; mean (SD) birth weight 1155 grams (± 284). Exclusion criteria: patients with recurrent bradycardia, second and third degree AV‐block, hypotension, refractory hypoglycaemia and major congenital malformations.
Interventions	Intervention group (n = 55 analysed): oral propranolol (1 mg/ml sterile water) at a dose of 0.5 mg/kg 12‐hourly. Control group (n = 54 analysed): placebo (calcium carbonate 1 mg/ml) at a dose of 0.5 mg/kg 12 hourly. Duration of treatment: from day 8 of life until 37 weeks' PMA or until complete retinal vascularisation; median (range) treatment duration 32 (7 to 72) days in the intervention group, 41 (1 to 107) days in the control group.
Outcomes	Primary outcome: All stages of ROP. Secondary outcomes: Adverse events such recurrent bradycardia, hypotension, hypoglycaemia. Incidence of laser therapy, rescue treatment with anti‐VEGF agents, visual outcome at 12 months' corrected age.
Notes	Registered retrospectively with ctri.nic.in CTRI/2013/11/004131. Dr Sanghvi (contact author) provided additional information on study methodology and data for subgroup analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random sequence.
Allocation concealment (selection bias)	Low risk	Study coordinator nurse had access to the opaque binder containing the prespecified sequence of allocation, provided by a statistician.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Care givers (physicians and nurses) were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors (ophthalmologist and physicians) were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	109 patients were randomised. In the intervention group, 4/55 (7%) infants died and in the control group, 3/54 (6%) infants died prior to first ROP screening. Further 22 patients (20%) were lost to visual follow‐up at 12 months' corrected age (secondary outcome).
Selective reporting (reporting bias)	Low risk	Primary outcome reported as specified in the trial protocol. Visual long‐term outcomes at 12 months' PMA were not prespecified in the trial protocol but reported. Trial was registered retrospectively.
Other bias	Low risk	None detected.