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 FEV1 after 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 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.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 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.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).

Safety of SABA Monotherapy in Asthma Management: a Systematic Review and Meta-analysis

“…A newly published double-blind, crossover, single-center, placebo-controlled non-inferiority study[ 30 ] compared the bronchodilator response to salbutamol and budesonide/formoterol in adults with stable asthma [ 30 ]. This study found no evidence of non-inferiority against a boundary of a forced expiratory volume in 1 s (FEV 1 ) of − 0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg at the timepoint of 2 min [ 30 ]. There were 33 adverse events reported among 22 participants [ 30 ].…”

“…This study found no evidence of non-inferiority against a boundary of a forced expiratory volume in 1 s (FEV 1 ) of − 0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg at the timepoint of 2 min [ 30 ]. There were 33 adverse events reported among 22 participants [ 30 ]. Only one adverse event (headache) was thought to be related to the administration of salbutamol [ 30 ].…”

“…There were 33 adverse events reported among 22 participants [ 30 ]. Only one adverse event (headache) was thought to be related to the administration of salbutamol [ 30 ]. A potential concern is that patients switching from SABA reliever therapy to budesonide/formoterol monotherapy may fail to achieve similar fast, effective, and safer symptom relief.…”

The Changing Asthma Management Landscape and Need for Appropriate SABA Prescription

“…A double-blind randomized controlled trial (RCT) has shown no difference between the bronchodilator effect of salbutamol and ICS-FOR in average forced expiratory volume in 1 s (FEV 1 ) achieved from first dose to a 90-min assessment point [mean ratio 98.4%; 95% confidence interval (CI) 91.6, 105.7; p = 0.66] [ 30 ]. In a different RCT, focusing on an earlier timepoint clinically relevant in terms of acute bronchodilation (2 min), the non-inferiority FEV 1 boundary of − 0.06 L for budesonide (BUD)-FOR compared with salbutamol was not met [ 31 ]; mean FEV 1 change from baseline 2 min after treatment administration was 0.08 L for BUD-FOR [standard deviation (SD) 0.14, n = 49] and 0.17 L for salbutamol (SD 0.18, n = 48) [ 31 ]. Over the 30 min post-dose, FEV 1 was higher with salbutamol than BUD-FOR (mean difference 0.10 L, p < 0.001); however, this was less than the suggested threshold for the minimum patient perceivable improvement of 0.23 L [ 32 ], and the study did not show any differences in perceived breathlessness between the treatments [ 31 ].…”

Quantitative CT Metrics for the Prediction of Therapeutic Effect in Asthma

“…Symbicort is a long-term maintenance medicine containing budesonide, a corticosteroid, and formoterol, a rapid and long-acting beta2-agonist, used twice daily to treat asthma in adults. The drug functions fifteen minutes after inhalation, providing a rapid, clinically effective bronchodilator response and relieving lung inflammation [ 13 , 14 ]. However, to our knowledge, no previous studies have assessed lung function during serial follow-ups in a predefined period, especially in exploring the medication effects and the correlation with airway measurement metrics.…”