Monograph

2. A Summary of the VESTRI Trial

A 6-month Safety and Benefit Study of Inhaled Fluticasone Propionate/ Salmeterol Combination Versus Inhaled Fluticasone Propionate in the Treatment of 6,200 Pediatric Subjects 4-11 Years Old With Persistent Asthma.


BACKGROUND
Long-acting beta-agonists (LABAs) have been known to increase the risk of asthma-related death in children and hospitalizations in adults. Recent meta-analyses demonstrated that the combination of LABAs and inhaled glucocorticoids in children reduced the risk of hospitalization. This trial investigated the safety (e.g. hospitalization, endotracheal intubation, death, etc.) of the combination of salmeterol (LABA) and fluticasone propionate (an inhaled glucocorticoid), i.e. Advair, in a fixed-dose combination.

METHODS
Children 4 to 11 who require daily asthma medications and had a history of asthma exacerbations in the previous year were randomly assigned in a 1:1 ratio to either: Advair at fixed-dose combinations (100/50mcg, 250/50mcg twice daily) OR Fluticasone alone (100mcg, 250mcg twice daily) for 26 weeks (approximately 6 months). The primary safety endpoint was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). The statistical design was looking for non-inferiority, where the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety endpoint was less than 2.675.

RESULTS
Among 6,208 patients, there were 27 patients in the Advair group and 21 in the fluticasone-alone group who had a serious asthma-related event and were hospitalized. The hazard ratio with Advair vs. fluticasone alone was 1.28 (95% CI 0.73-2.27), demonstrating that Advair was non-inferior (P=0.006). A total of 265 patients (8.5%) in the Advair group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI 0.73-1.01). There were no asthma-related deaths or intubations in the study. The data also demonstrated that the mean percentage of rescue therapy-free days was similar in patients taking salmeterol in a fixed-dose combination with fluticasone or fluticasone alone.

CONCLUSION
In children with asthma, there was a similar risk of a serious asthma-related event in patients taking salmeterol in a fixed-dose combination with fluticasone (Advair) or fluticasone alone. There was also a similar mean percentage of rescue therapy-free days in patients taking salmeterol in a fixed-dose combination with fluticasone (Advair) or fluticasone alone.

LIMITATIONS
The study was 6 months, and there were few adverse asthma-related events.

(Funding was provided by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344.)
Reference: https://clinicaltrials.gov/ct2/show/NCT01462344, Accessed Sept 10, 2016.