Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study

Abstract

Background: Clinical trials in children with moderate-to-severe persistent asthma are limited.

Objective: We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing.

Methods: The budesonide dose (with salmeterol [50 microg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 microg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction.

Results: Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated.

Conclusion: Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma.

Figure 1

Cascade of enrollment.

Figure 2

The Conditional power in MARS, calculated as the probability of rejecting the null hypothesis of no active treatment effect if the trial had reached the target enrollment (210 randomized children), given that the active treatment and placebo groups displayed approximately a 0.5 failure rates at the interim stage (55 randomized children).

Figure 3

Product-limit survival function estimates for time to return of inadequate control for children assigned to azithromycin (n=17), montelukast (n=19), and placebo (n=19).