Cade 2000.

Methods	Parallel design, 2‐arm Multi‐centre (5), conducted in the UK (West Yorkshire hospitals)
Participants	Inpatients Inclusion/exclusion criteria Inclusion criteria: age < 12 mo.; confirmed RSV; informed consent; randomised within 12 hours admission Exclusion criteria: history of hospitalisation with respiratory tract illness; chronic respiratory illness; congenital heart disease; prematurity; pre‐existing immunodeficiencies; recent exposure to varicella or tuberculosis; prolonged exposure to systemic glucocorticoids Participant characteristics All groups Sample size: randomised (N): 165, analysed ‐ trial primary outcome (N): 155 (ITT with available case analysis was used), analysed ‐ review primary outcome (N): 161 (ITT with available case analysis was used) GROUP 1 Sample size: randomised (N): 83, analysed ‐ trial primary outcome (N): 79, analysed ‐ review primary outcome (N): 82 Age, mean ± SD: 4.3 ± 2.8 Males, N (%): 45 (54.9) RSV status: all positive Atopic status: 43/82 present (infant) GROUP 2 Sample size: randomised (N): 82, analysed ‐ trial primary outcome (N): 76, analysed ‐ review primary outcome (N): 79 Age, mean ± SD: 4.0 ± 2.8 Males, N (%): 47 (59.5) RSV status: all positive Atopic status: 38/79 present (infant)
Interventions	GROUP 1 (with glucocorticoid) Drug name: budesonide Dose: 1 mg Mode of administration: nebulised 10 minutes Timing/duration: twice daily, 14 to 21 days GROUP 2 Drug name: placebo (NR) Dose: NR Mode of administration: nebulised 10 minutes Timing/duration: twice daily, 14 to 21 days Additional co‐interventions for all groups: 6.5 L/minute O2 therapy; reported use of ipratropium bromide, B2 agonists, oral/IV glucocorticoids, antibiotics Protocolised use of bronchodilators with glucocorticoids: no
Outcomes	Primary outcome/outcome used to calculate sample size Coughing or wheezing episodes (within 12 mo.; proportion with at least 1 episode) Secondary outcomes LOS; clinical scale developed for this trial ‐ 11‐point score, based on heart rate, respiratory rate, supplemental oxygen requirements, and the presence or absence of chest wall retractions*; additional medication use*#; hospital readmission#; return healthcare visits#; respiratory symptoms# *time points: during hospitalisation #time points: first 28 days, by 12 months (personal diaries, nurse visits, medical records)
Funding	Astra Foundation ‐ full financial support grant
Notes	Study reported analyses of some outcomes by initial severity score, duration of symptoms at presentation, atopic history and exposure to cigarette smoke or damp in the household; no specific interaction term This study contributed to the following comparisons in this review: steroid versus placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"...infants were randomised to receive either treatment or placebo. Randomisation was stratified by sex and centre." No further information provided
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) Health care use ((re)admissions, LOS, return visits)	Unclear risk	"the trial solution and side stream nebulisers were manufactured and packaged to ensure the double‐blind nature of the study"; as no further information provided, and both random sequence generation and allocation concealment were unclear, we considered blinding unclear
Blinding (performance bias and detection bias) Patient/parent‐reported outcomes (symptoms, QoL)	Unclear risk	"the trial solution and side stream nebulisers were manufactured and packaged to ensure the double‐blind nature of the study"; as no further information provided, and both random sequence generation and allocation concealment were unclear, we considered blinding unclear
Blinding (performance bias and detection bias) Other outcomes (adverse events, others)	Unclear risk	"the trial solution and side stream nebulisers were manufactured and packaged to ensure the double‐blind nature of the study"; as no further information provided, and both random sequence generation and allocation concealment were unclear, we considered blinding unclear
Incomplete outcome data (attrition bias) Health care use ((re)admissions, LOS, return visits)	Low risk	3 exclusions post‐randomisation, motives reported, balanced between groups
Incomplete outcome data (attrition bias) Patient/parent‐reported outcomes (symptoms, QoL)	Unclear risk	Data on parental diaries reported in 79/83 and 76/82 participants, of which 96% and 98% were complete, respectively; apparently there is a mismatch with the absolute numbers presented; no motives for incomplete outcome data reported
Incomplete outcome data (attrition bias) Other outcomes (adverse events, others)	Low risk	3 exclusions post‐randomisation, motives reported, balanced between groups
Selective reporting (reporting bias)	High risk	Published report includes all pre‐specified and expected outcomes; however, "length of time until symptom free" definition was changed due to incomplete outcome data; the study protocol was not available
Other bias	Low risk	No significant baseline imbalances; no other sources of bias
Overall risk of bias	High risk	> 1 domain as high risk of bias