Austri, a Large Randomized Study in Adolescents and Adults with Asthma, Assessing the Safety and Efficacy of Salmeterol in Combination with Fluticasone Propionate Compared to Fluticasone Propionate Alone

Rationale: Previous studies have shown an excess of serious asthma-related outcomes, including death, in subjects taking Long Acting Beta Agonists (LABAs). This study was designed to examine the risks and/or benefits of LABA therapy when added to an ICS in a combination inhaler in patients with asthma.

Methods: A global, randomized, double-blind, parallel group study of asthmatic subjects ≥12 years; treated with salmeterol (SAL) and fluticasone propionate (FP) in combination (FSC) or FP alone for 26 weeks. The primary endpoint was time to first serious asthma-related event, the composite of death, intubation or hospitalization. To declare non-inferiority the hazard ratio of subjects with a serious asthma-related event with FSC compared to FP was <2.0 based on the upper bound of the 95% confidence interval (CI) on the estimate of the hazard ratio. The secondary endpoint was time to first asthma exacerbation requiring OCS.

Results: Of 11,751 subjects randomized, 67 subjects experienced 74 serious asthma-related events with 34 and 33 subjects treated with FSC and FP, respectively. The FSC/FP hazard ratio was 1.029 (0.638-1.662) for time to first serious asthma-related event. Non-inferiority was achieved. There were no asthma-related deaths and 2 asthma-related intubations (both on FP). The FSC/FP hazard ratio for time to first asthma exacerbation was 0.787 (0.698-0.888).

Conclusions: There was no evidence of an increased risk of serious asthma-related events when SAL was used in a combination product with FP compared to FP.  There was a significant reduction in risk of asthma exacerbations for FSC compared to FP alone.