Fok 1999.

Methods	Randomised controlled trial. Blinding of randomisation: yes Blinding of intervention: yes Complete follow‐up: yes Blinding of outcome measurement: can't tell
Participants	Preterm infants < 32 weeks gestational age, birth weight < 1.5 kg and requiring mechanical ventilation were eligible if 6 to 10 hours after the second dose of surfactant the arterial PO₂:alveolar PO₂ was < 0.25. Demographic data: values are presented as mean (SD) Fluticasone propionate group: n = 27 Birth weight (g): 993 (369) Gestational age (weeks): 27.9 (2.6) arterial PO₂: alveolar PO₂ ratio at enrolment: 0.19 (0.05) Placebo group: n = 26 Birth weight (g): 981 (362) Gestational age (weeks): 27.1 (2.6) arterial PO₂: alveolar PO₂ ratio at enrolment: 0.19 (0.05) Exclusion criteria: Infants who were dying and those with significant congenital anomalies were excluded. Study centre: Hong Kong, China Study period: not stated
Interventions	Fluticasone propionate group (n = 27) Placebo group (n = 26) Mode of delivery: aerosol delivery was carried out using an MV15s Aerochamber inserted between the Y‐connector of the ventilator circuit and endotracheal tube. Infants extubated before day 14 received aerosol through a neonatal Aerochamber (Trudell, Canada), which was modified by removing its one way non‐rebreathing valve. This modification has been shown to increase the amount of aerosol delivery. The face mask of Aerochamber was replaced with a Laerdal Resuscitation mask (Laerdal, Stavanger, Norway) as it has a smaller dead space and a tighter fit to the face. Dose: two puffs of Fluticasone propionate (Flixotide; Glaxo, UK; 250 µg/ puff) or placebo by metered dose inhaler 12 hourly. Duration of treatment: 2 weeks. The first dose was given within 24 hours of birth.
Outcomes	Primary outcomes: Successful extubation by days 7 and 14 of age Secondary outcomes: Mortality Oxygen dependency at 28 days of postnatal age and 36 weeks' PMA Adverse events: hyperglycaemia, hypertension, sepsis confirmed by blood culture, pulmonary air leak (interstitial emphysema, pneumothorax, or pneumomediastinum), periventricular haemorrhage and leukomalacia, ROP, PDA, NEC and bacterial colonization of the airway Hyperglycemia was defined as a blood glucose reading > 7 mmol/L. Hypertension was defined as 2 consecutive readings of systolic or diastolic blood pressure ˃ 80 mmHg and 45 mmHg respectively. Symptomatic PDA was treated with intravenous indomethacin after confirmation by echocardiogram and refractory duct was closed by surgical ligation. Cranial ultrasound scans were performed at 6, 14 and 28 days of age, and when periventricular haemorrhage was suspected clinically. Ophthalmology screening for ROP was started at 4 weeks of age. NEC was diagnosed by the presence of pneumatosis intestinalis or intestinal perforation on abdominal radiograph, of for those requiring surgical intervention, on laparotomy. Tracheal aspirates for bacterial and fungal cultures were obtained immediately before the first dose of aerosol, and at 3, 5, 7 and 14 days of age. Static respiratory system compliance (Crs) and resistance (Rrs) were measured immediately before the start of aerosol treatment, and repeated on days 3, 7, and 14 in infants who remained intubated and ventilated. Both Crs and Rrs were measured using a SensorMedics Pulmonary Cart (SensorMedics Inc., Yorba Linda, CA, USA) using the passive flow‐volume technique. The measurement were carried out using a pneumotachograph (Hans Rudolph Inc., USA) with a small dead space (1.8 ml) connected to the endotracheal tube.
Notes	Infants were randomised using computer‐generated random numbers into treatment and control groups and allocation to the groups was performed using opaque, sealed envelopes. All infants were given two doses (5 ml/kg/dose) of intratracheal synthetic surfactant (Exosurf) 12 hours apart. The first dose was given within 1 hour of birth. Extubation was considered when the FiO₂ and ventilator rate decreased to < 0.4 and < 10 breaths/minute, respectively. The decision to extubate was made by the attending neonatologists who were blinded to the study protocol and the nature of the aerosol given to the infants. All infants were given a loading dose of intravenous aminophylline (6 mg/kg) prior to extubation followed by a maintenance dose of 2.5 mg/kg every 12 hourly. Extubation was considered successful if the infant was able to breathe spontaneously without the endotracheal tube or assisted ventilation for at least 48 hours without a significant increase in respiratory effort and deterioration in blood gas values. In both groups infants with significant respiratory problems after 14 days of age were given open label systemic dexamethasone as decided by the attending neonatologists.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised controlled trial Method of sequence generation unknown
Allocation concealment (selection bias)	Low risk	Blinding of randomisation: yes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of intervention: yes
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding of outcome measurement: can't tell
Incomplete outcome data (attrition bias) All outcomes	Low risk	Complete follow‐up: yes
Selective reporting (reporting bias)	Unclear risk	The trial was not registered so we cannot tell if there was selective reporting or not.
Other bias	Low risk	Appears free of other bias.