Repeated dose budesonide/formoterol compared to salbutamol in adult asthma: A randomised cross-over trial.

Abstract

To determine the comparative bronchodilator, systemic beta2-agonist, cardiovascular and adverse effects of salbutamol 200 µg and budesonide/formoterol 200/6 µg when taken repeatedly in stable asthma. This open-label, cross-over, single-centre, controlled trial, randomised adults with asthma to different orders of two treatment regimens: salbutamol 200 µg via MDI at t=0, 30, 60, 90 min, then salbutamol 2.5 mg via nebuliser at t=120, 140, 160 and 420 min; or budesonide/formoterol 200/6 µg one actuation via Turbuhaler at t=0, 30, 60, 90 min, two actuations at t=120, 140, 160 and 420 min. The primary outcome measure was FEV1 after 180 min. Secondary outcomes included repeat measures of FEV1, serum potassium, heart rate, and adverse events RESULTS: Of 39 patients randomised, two withdrew due to adverse events (QTCF prolongation and T wave abnormalities) after the first intervention with salbutamol. The mean (sd) change from baseline FEV1 180 min after randomisation for salbutamol and budesonide/formoterol regimens was 0.71 (0.46) L, N=38, and 0.58 (0.45) L, N=37, respectively; with a mean (sd) paired difference of -0.10 (0.40) L, N=37, and a model-based estimated difference (95% CI) -0.12 (-0.25 to 0.02) L, p=0.088. In the main secondary analysis, salbutamol resulted in significantly greater FEV1 from 30 to 240 min, but lesser FEV1 at 360 and 420 min. Salbutamol resulted in a significantly lower serum potassium, and a higher heart rate and number of adverse events. The comparative bronchodilator responses of repeated administration of salbutamol 200 µg dose-1 and budesonide/formoterol 200/6 µg differed depending on the time of measurement. Salbutamol caused greater systemic beta2-agonist and cardiovascular effects and more adverse events.