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

Robert C. Strunk, Leonard B. Bacharier, Brenda R. Phillips, Stanley J. Szefler, Robert S. Zeiger, Vernon M. Chinchilli, Fernando Martinez, Robert F. Lemanske, Lynn M. Taussig, David T. Mauger, Wayne J Morgan, Christine A. Sorkness, Ian M. Paul, Theresa Guilbert, Marzena Krawiec, Ronina Covar, Gary Larsen

Research output: Contribution to journalArticle

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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 μg] 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 μg 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number6
DOIs
StatePublished - Dec 2008

Fingerprint

montelukast
Azithromycin
Budesonide
Adrenal Cortex Hormones
Asthma
Medical Futility
Placebos
Random Allocation
Clinical Trials Data Monitoring Committees
Sample Size
Multicenter Studies
Clinical Trials

Keywords

  • Asthma
  • children
  • clinical trial
  • leukotriene receptor antagonist
  • macrolide
  • moderate to severe

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Strunk, R. C., Bacharier, L. B., Phillips, B. R., Szefler, S. J., Zeiger, R. S., Chinchilli, V. M., ... Larsen, G. (2008). Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. Journal of Allergy and Clinical Immunology, 122(6). https://doi.org/10.1016/j.jaci.2008.09.028

Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. / Strunk, Robert C.; Bacharier, Leonard B.; Phillips, Brenda R.; Szefler, Stanley J.; Zeiger, Robert S.; Chinchilli, Vernon M.; Martinez, Fernando; Lemanske, Robert F.; Taussig, Lynn M.; Mauger, David T.; Morgan, Wayne J; Sorkness, Christine A.; Paul, Ian M.; Guilbert, Theresa; Krawiec, Marzena; Covar, Ronina; Larsen, Gary.

In: Journal of Allergy and Clinical Immunology, Vol. 122, No. 6, 12.2008.

Research output: Contribution to journalArticle

Strunk, RC, Bacharier, LB, Phillips, BR, Szefler, SJ, Zeiger, RS, Chinchilli, VM, Martinez, F, Lemanske, RF, Taussig, LM, Mauger, DT, Morgan, WJ, Sorkness, CA, Paul, IM, Guilbert, T, Krawiec, M, Covar, R & Larsen, G 2008, 'Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study', Journal of Allergy and Clinical Immunology, vol. 122, no. 6. https://doi.org/10.1016/j.jaci.2008.09.028
Strunk, Robert C. ; Bacharier, Leonard B. ; Phillips, Brenda R. ; Szefler, Stanley J. ; Zeiger, Robert S. ; Chinchilli, Vernon M. ; Martinez, Fernando ; Lemanske, Robert F. ; Taussig, Lynn M. ; Mauger, David T. ; Morgan, Wayne J ; Sorkness, Christine A. ; Paul, Ian M. ; Guilbert, Theresa ; Krawiec, Marzena ; Covar, Ronina ; Larsen, Gary. / Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. In: Journal of Allergy and Clinical Immunology. 2008 ; Vol. 122, No. 6.
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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 μg] 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 μg 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.",
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AU - Szefler, Stanley J.

AU - Zeiger, Robert S.

AU - Chinchilli, Vernon M.

AU - Martinez, Fernando

AU - Lemanske, Robert F.

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AU - Mauger, David T.

AU - Morgan, Wayne J

AU - Sorkness, Christine A.

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