A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

doi:10.1016/j.jaci.2009.11.015

Journal of Allergy and Clinical Immunology

Volume 125, Issue 2, February 2010, Pages 374-380

https://doi.org/10.1016/j.jaci.2009.11.015 Get rights and content

Background

Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies.

Objective

To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma.

Methods

A total of 583 adults with acute asthma were treated with standard care during a ≤60-minute screening period. Patients with FEV₁ ≤50% predicted were randomly allocated to intravenous montelukast 7 mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind treatment period lasted until a decision for discharge, hospital admission, or discontinuation from the study. The primary efficacy endpoint was the time-weighted average change in FEV₁ during 60 minutes after drug administration. Secondary endpoints included the time-weighted average change in FEV₁ at various intervals (10-120 minutes) and percentage of patients with treatment failure (defined as hospitalization or lack of decision to discharge by 3 hours postadministration).

Results

Montelukast significantly increased FEV₁ at 60 minutes postdose; the difference between change from baseline for placebo (least-squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI, 0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV₁-related variables were seen at all time points (all P <.05). Although treatment failure did not differ between groups (OR 0.92; 95% CI, 0.63, 1.34), a prespecified subgroup analysis suggests likely benefit for intravenous montelukast at US sites.

Conclusion

Intravenous montelukast added to standard care in adults with acute asthma produced significant relief of airway obstruction throughout the 2 hours after administration, with an onset of action as early as 10 minutes.

Section snippets

Patients and study design

This study was conducted between July 2004 and February 2007 in the United States (34 sites) and 15 other countries (28 sites). Subjects were ≥15 years old, had ≥1 year history of physician-diagnosed asthma, and presented with an acute exacerbation of asthma. Patients >54 years were included if they also had documented FEV₁ reversibility ≥15% after β₂-agonist treatment during the current episode or within the past 5 years, or if their lifetime tobacco exposure was ≤10 pack-years. Exclusion

Patients and baseline characteristics

Of 1147 patients screened, 583 were randomly assigned to treatment (Fig 1). A total of 573 patients (98%) completed the study. Of those randomized, 12 of 583 (2.1%: 4 montelukast, 8 placebo) were excluded from the primary analysis for not having a baseline FEV₁ measurement. Baseline characteristics of patients were similar between the treatment groups (Table I).

Efficacy

Compared with placebo, montelukast produced a significantly larger improvement of FEV₁ throughout the 2 hours after administration in

Discussion

In this randomized, double-blind, placebo-controlled study of almost 600 adults with acute asthma, we found that intravenous montelukast, when added to standard therapy, provided significant, rapid, and sustained benefit in acute asthma, as indicated by relief of airway obstruction. The average changes in FEV₁ during the first 60 minutes (primary endpoint), at 120, 40, 20, and 10 minutes, and over the time interval until a disposition decision was made were all significantly greater with

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: Supported by Merck & Co, Inc.

: Disclosure of potential conflict of interest: C. A. Camargo has received financial support for consulting, lectures, advisory boards, and medical research for many groups, including AstraZeneca, Dey, GlaxoSmithKline, Merck, and Novartis. L. M. Fabbri receives fees for lecturing, consultancies, and advisory boards from Nycomed, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche, and Pfizer. D. M. Gurner, S. A. Green, M.-P. Malice, C. Legrand, S. B. Dass, B. A. Knorr, and T. F. Reiss are employed by Merck and Co, Inc. The rest of the authors have declared that they have no conflict of interest.

: Clinical Trials registration: NCT00092989: http://www.clinicaltrials.gov/ct2/show/NCT00092989?term=NCT00092989&rank=1

View full text

Asthma and lower airway diseaseA randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

Background

Objective

Methods

Results

Conclusion

Section snippets

Patients and study design

Patients and baseline characteristics

Efficacy

Discussion

Chest

Clin Chest Med

Chest

Am J Med

Chest

Chest

Inflammatory events in severe acute asthma

Allergy

Acute severe asthma

Am J Respir Crit Care Med

Antileukotrienes as adjunctive therapy in acute asthma

Drugs

Montelukast in the treatment of asthma as a systemic disease

Expert Rev Clin Immonol

A review of montelukast in the treatment of asthma and allergic rhinitis

Expert Opin Pharmacother

Clinical efficacy of montelukast in adults and children

Clin Exp Allergy Rev

Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma

Thorax

Asthma and lower airway disease
A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma