The Journal of Allergy and Clinical Immunology
Volume 122, Issue 6 , Pages 1138-1144.e4, December 2008

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

  • Robert C. Strunk, MD

      Affiliations

    • Department of Pediatrics, Washington University and St Louis Children's Hospital, St Louis, Mo
    • Corresponding Author InformationReprint requests: Robert C. Strunk, MD, 1 Children's Place, St Louis, MO 63110.
    • ,
  • Leonard B. Bacharier, MD

      Affiliations

    • Department of Pediatrics, Washington University and St Louis Children's Hospital, St Louis, Mo
    • ,
  • Brenda R. Phillips, MS

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Stanley J. Szefler, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Robert S. Zeiger, MD, PhD

      Affiliations

    • Department of Pediatrics, University of California–San Diego, San Diego, Calif
    • Department of Allergy, Kaiser Permanente Southern California, San Diego, Calif
    • ,
  • Vernon M. Chinchilli, PhD

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Fernando D. Martinez, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson, Ariz
    • ,
  • Robert F. Lemanske Jr., MD

      Affiliations

    • Departments of Medicine and Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis
    • ,
  • Lynn M. Taussig, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo
    • ,
  • David T. Mauger, PhD

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Wayne J. Morgan, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson, Ariz
    • ,
  • Christine A. Sorkness, PharmD

      Affiliations

    • Schools of Pharmacy, Medicine, and Public Health, University of Wisconsin, Madison, Wis
    • ,
  • Ian M. Paul, MD

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Theresa Guilbert, MD

      Affiliations

    • Department of Pediatrics, University of Wisconsin School of Medicine, Madison, Wis
    • ,
  • Marzena Krawiec, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Ronina Covar, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Gary Larsen, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo
    • ,
  • Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute

      Affiliations

    • See Appendix E1 in this article's Online Repository at www.jacionline.org for a list of the Childhood Asthma Research and Education Network members.

Received 26 March 2008; received in revised form 20 August 2008; accepted 15 September 2008. published online 28 October 2008.

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.

Key words: Asthma, moderate to severe, children, macrolide, leukotriene receptor antagonist, clinical trial

Abbreviations used: CARE, Childhood Asthma Research and Education, DSMB, Data Safety Monitoring Board, ICS, Inhaled corticosteroid, MARS, Montelukast or Azithromycin for Reduction of Inhaled Corticosteroids in Childhood Asthma, OCS, Oral corticosteroid, PEF, Peak expiratory flow

 

 Disclosure of potential conflict of interest: L. B. Bacharier has received honoraria from AstraZeneca, Genentech, GlaxoSmithKline, Merck, and Aerocrine and has served on an advisory board for Schering-Plough. S. J. Szefler has served as a consultant for AstraZeneca, GlaxoSmithKline, Aventis, Genentech, and Merck and has received research support from the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute (NHLBI), and Ross Pharmaceuticals. R. S. Zeiger has served as a consultant for Aerocrine, AstraZeneca, GlaxoSmithKline, Genentech, Merck, Schering, and Novartis and has received research support from Sanofi Aventis and Genentech. V. M. Chinchilli has received research support from the NIH and NHLBI. F. D. Martinez has received lecture fees from and has served on an advisory board for Merck and has served as a consultant for GlaxoSmithKline. R. F. Lemanske has received speaker honoraria from Merck; has served as a consultant for MAP Pharmaceuticals; and has received research support from the NHLBI. D. T. Mauger has received research support from the NIH. W. J. Morgan has served as a consultant for the Cystic Fibrosis Foundation and Genentech and has received research support from the NIH. C. A. Sorkness has served as a consultant for GlaxoSmithKline and Novartis and has received research support from Novartis, the NHLBI, and the National Institute of Allergy and Infectious Diseases (NIAID). I. M. Paul has served as a consultant for McNeil Consumer Healthcare, the Consumer Healthcare Products Association, and Reckitt Brackiser Healthcare International and has received research support from GlaxoSmithKline, the National Honey Board, and Johnson & Johnson. T. Guilbert has received honoraria for serving as a consultant, speaker, or both for GlaxoSmithKline, AstraZeneca, Merck, and Antidote (formerly World Medical Conferences CME Programs) and has received research support from Altus Pharmaceuticals, Inspire Pharmaceuticals, and the NIH. M. Krawiec has served on the speakers' bureau for Merck and GlaxoSmithKline; has served as a consultant on a peer-reviewed publication for Adelphi; has served as a consultant for Parexel and Novartis; and has provided legal consultation or expert witness testimony on the topic of pediatric asthma. R. Covar has served as a consultant for Merck and has received research funding from Ross Abbott Laboratories and AstraZeneca. G. Larsen has served on an asthma advisory board for Genentech and has received research funding from the NIH. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(08)01723-5

doi:10.1016/j.jaci.2008.09.028

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 6 , Pages 1138-1144.e4, December 2008

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