Budesonide–formoterol versus salbutamol as reliever therapy in children with mild asthma (CARE): a 52-week, open-label, multicentre, superiority, randomised controlled trial

Background: Combination inhaled corticosteroid–formoterol reliever monotherapy reduces the rate of asthma attacks compared to short-acting β₂-agonist (SABA) reliever monotherapy in adults. Its comparative efficacy in children has not been established. Methods: CARE was a 52-week, open-label, parallel-group, multicentre, superiority, randomised controlled trial in children aged 5–15 years with asthma using SABA reliever monotherapy at 15 clinical trials sites in New Zealand. Participants were randomly assigned (1:1) to either budesonide 50 μg–formoterol 3 μg, two actuations as needed, or salbutamol 100 μg, two actuations as needed. The primary outcome was asthma attacks as rate per participant per year. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12620001091998. Findings: From Jan 28, 2021, to June 23, 2023, we assessed 382 participants for eligibility. We randomly assigned 360 (94%) participants to treatment (179 [50%] to the budesonide–formoterol group and 181 [50%] to the salbutamol group). The annualised rate of asthma attacks was lower in the budesonide–formoterol group than in the salbutamol group—cluster-adjusted rates 0·23 versus 0·41 per participant per year (relative rate 0·55 [95% CI 0·35–0·86]; p=0·012). The number of participants with at least one adverse event was 162 (91%) in the budesonide–formoterol group and 167 (92%) in the salbutamol group (odds ratio 0·79 [95% CI 0·35–1·79]). Interpretation: In children aged 5–15 years with mild asthma, budesonide–formoterol reliever monotherapy is superior to salbutamol for preventing asthma attacks, with a similar safety profile. Funding: Health Research Council of New Zealand, Cure Kids New Zealand, and the Barbara Basham Medical Charitable Trust (managed by Perpetual Guardian).