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

Abstract

To compare bronchodilator response after to salbutamol and budesonide/formoterol in adults with stable asthma. A 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 FEV₁ after 2 min. Secondary outcome measures included FEV₁, mBorg Dyspnoea Scale score and visual analogue score for breathlessness over 30 min. Forty-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 FEV₁ 2 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, FEV₁ over 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. The 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 FEV₁ at 2 min, and could be consistent with inferiority with a p value of 0.07. For the secondary analysis of FEV₁ measurements over time, the FEV₁ was higher with salbutamol. Australian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).