Characteristics of included studies
| Study, first author (year) | Design | Duration | Sites | Population | Participants (intervention versus control)# n | Primary outcome (analysis) | Intervention | Control |
| SYGMA 1 O’Byrne (2018) | RCT, parallel-group, double-blind placebo-controlled | 52 weeks | 261 sites, 18 countries | Adults and adolescents (≥12 years) | 2559 (1277 versus 1282) | Mean percentage of electronically recorded weeks with well-controlled asthma per patient (noninferiority)¶ | Budesonide-formoterol 200/6 μg (Symbicort Turbuhaler, AstraZeneca) one inhalation as needed plus twice-daily placebo | Budesonide 200 μg (Pulmicort Turbuhaler, AstraZeneca) twice daily plus terbutaline 500 μg (Turbuhaler) as needed |
| SYGMA 2 Bateman (2018) | RCT, parallel-group, double-blind placebo-controlled | 52 weeks | 350 sites, 25 countries | Adults and adolescents (≥12 years) | 4176 (2089 versus 2087) | Annualised rate of severe exacerbations (non-inferiority)+ | Budesonide-formoterol 200/6 μg (Symbicort Turbuhaler, AstraZeneca) one inhalation as needed plus twice-daily placebo | Budesonide 200 μg (Pulmicort Turbuhaler, AstraZeneca) twice daily plus terbutaline 500 μg (Turbuhaler) as needed |
| Novel start Beasley (2019) | RCT, parallel-group, open-label, real-world | 52 weeks | 16 sites, 4 countries | Adults (≥18 years) | 425 (220 versus 225) | Annualised rate of asthma exacerbations (superiority) | Budesonide-formoterol 200/6 μg (Symbicort Turbuhaler, AstraZeneca) one inhalation as-needed | Budesonide 200 μg (Pulmicort Turbuhaler, AstraZeneca) twice daily plus albuterol 100 μg (Ventolin pMDI) two inhalations as needed |
| PRACTICAL Hardy (2019) | RCT, parallel-group, open-label, real-world | 52 weeks | 15 sites, 1 country | Adults and adolescents (≥18 years) | 885 (437 versus 448) | Number of severe exacerbations per patient per year (superiority) | Budesonide-formoterol 200/6 μg (Symbicort Turbuhaler, AstraZeneca) one inhalation as needed | Budesonide 200 μg (Pulmicort Turbuhaler, AstraZeneca) twice daily plus terbutaline 250 μg (Bricanyl Turbuhaler, AstraZeneca) two inhalations as needed |
This table does not include details of additional trial arms, which were present in the SYGMA 1 and Novel START studies. All information derived from published trial protocols (including trial registries), manuscripts and supplementary material. RCT: randomised controlled trial; pMDI: pressurised metered-dose inhaler. #: intervention refers to as-needed budesonide-formoterol, control refers to maintenance budesonide plus short-acting β2-agonist (SABA) reliever. Participant numbers refer to as-needed inhaled corticosteroid (ICS)-formoterol and maintenance ICS plus SABA arms only; numbers for SABA only arms in SYGMA 1 and Novel START not included; ¶: superiority analysis for as-needed budesonide-formoterol versus SABA (primary), and noninferiority analysis for as-needed budesonide-formoterol versus maintenance budesonide plus SABA (secondary); +: initially superiority.