Chest
Volume 126, Issue 5, November 2004, Pages 1480-1489
Journal home page for Chest

Clinical Investigations
ASTHMA
Zafirlukast Treatment for Acute Asthma: Evaluation in a Randomized, Double-Blind, Multicenter Trial

https://doi.org/10.1378/chest.126.5.1480Get rights and content

Context:

Acute asthma causes nearly 2 million hospital emergency department (ED) visits in the United States annually, and hospitalization after an ED visit and relapse after ED discharge are common.

Objective:

To evaluate the adding of therapy with zafirlukast to standardized care for patients with acute asthma in the ED and a 28-day follow-up period.

Design and patients:

A total of 641 patients presenting to the ED with acute asthma were randomized to receive either single-dose zafirlukast, 160 mg (Z160) [162 patients], zafirlukast, 20 mg (Z20) [158 patients]), or placebo (321 patients) as adjunct treatment to standard care in this double-blind, multicenter trial. Assessments, including spirometry and symptom scores, were obtained before each albuterol treatment and at 4 h. Patients who were discharged from the ED after 4 h continued outpatient therapy over a 28-day period and received either Z20 bid (276 patients) or placebo (270 patients) in addition to prednisone, albuterol, and their previous asthma medications. FEV1 was measured at clinic visits on days 10 and 28. Patients recorded outpatient clinical data twice daily on a home diary card.

Main outcome measures:

the effect of zafirlukast on relapse after ED discharge. Other assessments were the rate of extended care (ie, ED stay for > 4 h or hospitalization), FEV1, and symptoms.

Results:

At the end of the outpatient period, 65 of 276 patients (23.6%) treated with zafirlukast and 78 of 270 patients (28.9%) treated with placebo relapsed (p = 0.047; absolute reduction, 5.3%; relative reduction, 18.3%). At the end of the ED period, 16 of 162 patients (9.9%) treated with Z160, 26 of 158 patients (16.5%) treated with Z20, and 48 of 321 patients (15.0%) treated with placebo required extended care (p = 0.052; absolute reduction with Z160 compared to placebo, 5.1%; relative reduction, 34%). These findings were supported by a significant improvement in FEV1 and dyspnea in the ED with the use of Z160 therapy, and by greater improvement in FEV1 and symptoms during the outpatient period for patients treated with Z20.

Conclusions:

When added to standardized care, therapy with Z20 bid reduced the risk of relapse compared with placebo over a 28-day treatment period. One dose of Z160 in the ED also reduced the rate of extended care.

Section snippets

Materials and Methods

This trial was conducted in 20 US hospital-affiliated EDs. Patients aged 12 to 65 years who presented to the ED with acute asthma were screened by study investigators for trial eligibility. Eligible patients were those with a history of asthma and a FEV1 of < 70% predicted both at ED entry and 25 min after receiving a single aerosol treatment with 2.5 mg of albuterol. Patients with the following conditions were excluded from the study: history of smoking of > 10 pack-years; positive pregnancy

Patients

During the ED period, 641 patients were randomized to treatment as follows: Z160, 162 patients; Z20, 158 patients; and placebo, 321 patients (Fig 2). Demographic and disease characteristics at ED entry are presented in Table 1. The mean age was 32 years, and the mean FEV1 was 37.8% predicted. At the end of the ED period, 551 of 641 patients (86%) were discharged from the ED, and 546 patients entered the outpatient period. Of those, 276 were treated with Z20 bid and 270 were treated with placebo

Discussion

Previous studies10,11 have suggested that cysteinyl leukotrienes have a role in the pathophysiology of acute asthma. This multicenter trial showed that adding a leukotriene receptor antagonist to standardized ED therapy and routine discharge medication decreases the need for extended care in the ED and improves the 28-day outpatient relapse rate. Improvement in asthma symptoms and airway function occurred with the first dose in the ED, and many secondary outcomes improved throughout the trial.

Steering Committee

Robert Silverman, MD (Chair); Richard Nowak, MD; Emil Skobeloff, MD; Phillip Korenblat, MD; and Steven Simonson, MD.

Investigators

Leonard Altman, MD, Harbor View Medical Center, Seattle, WA; Paula J. Anderson, MD, University of Arkansas for Medical Sciences, Little Rock, AR; Raymond E. Brady, MD, Vancouver, WA; Ronald A. Charles, MD, Parkland Hospital, UT Southwestern Medical Center, Dallas, TX; William Calhoun, MD, Presbyterian University Hospital, University of Pittsburgh, Pittsburgh, PA; Charles Emerman,

ACKNOWLEDGMENT

The authors thank Jean Fennimore, BS, RN, Mike Koeferl, PhD, and Scott Tutak, BS, for trial initiation and management support, Susan Beatty, MD, for medical consultation, Marshall Joffe MD, PhD, for statistical review and propensity analysis, Suzanne Bristow-Marcalus, BSPharm, ELS, and Jeanne McFadden, ELS, for editorial and graphic assistance, and Kathy Walsh, eResearch Technology, Inc. (formerly Premier Research Worldwide, Philadelphia, PA), for assistance with the spirometry.

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This trial was supported by AstraZeneca (Wilmington, DE).

Drs. Silverman and Korenblat have served as consultants for AstraZeneca, Drs. Korenblat and Nowak are on the AstraZeneca speakers committee, and Drs. Simonson, Bonucelli, and Chen, and Mr. Miller are employees of AstraZeneca.

Currently with Consortium Clinical Research, Upland, PA.

A list of participating investigators and centers is located in the Appendix.

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