Single dose of budesonide/formoterol turbuhaler compared to salbutamol pMDI for speed of bronchodilator onset in asthma: a randomised cross-over trial

Abstract

ObjectiveTo compare bronchodilator response after to salbutamol and budesonide/formoterol in adults with stable asthma.MethodsA double-blind, cross-over, single-centre, placebo-controlled, non-inferiority trial. Adults with stable asthma were randomised to different orders of two treatment regimens: two actuations of placebo via MDI and one actuation of budesonide/formoterol 200/6 µg via turbuhaler; and one actuation of placebo turbuhaler and two actuations of salbutamol 100 µg via MDI. The primary outcome measure was FEV1after 2 min. Secondary outcome measures included FEV1, mBorg Dyspnoea Scale score and visual analogue score for breathlessness over 30 min.ResultsForty-nine of 50 potential participants were randomised. One participant withdrew following the first intervention visit and another could not be randomised due to COVID-19 restrictions. The mean (SD) change from baseline FEV12 min after treatment administration for budesonide/formoterol and salbutamol was 0.08 (0.14) L, n=49, and 0.17 (0.18) L, n=48, respectively, mean (95% CI) paired difference of −0.097 L (−0.147 to −0.047), p=0.07, against a non-inferiority bound of −0.06 L. In the secondary analysis, FEV1over 30 min was lower for budesonide/formoterol compared with salbutamol, difference (95% CI): −0.10 (−0.12 to −0.08) L, p<0.001. There were no differences in Visual Analogue Scale score or mBorg Dyspnoea Scale score between treatments.ConclusionThe results do not support the primary hypothesis of non-inferiority at the boundary of −0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg for FEV1at 2 min, and could be consistent with inferiority with a p value of 0.07. For the secondary analysis of FEV1measurements over time, the FEV1was higher with salbutamol.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).