Fluticasone Propionate Compared with Zafirlukast in Controlling Persistent Asthma A Randomized Double-Blind, Placebo-Controlled Trial

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Original Research

Fluticasone Propionate Compared with Zafirlukast in Controlling Persistent Asthma A Randomized Double-Blind, Placebo-Controlled Trial

J Fam Pract. 2001 July;50(7):595-602

By

William Busse, MD

References

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OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma.

STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo.

POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone.

OUTCOMES MEASURED: Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results.

RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%).

CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.

Asthma, a chronic inflammatory disorder of the airways, affects approximately 17.3 million people in the United States, with more than 5000 deaths per year attributed to the disorder.¹ National Institutes of Health (NIH) guidelines for asthma management recommend that patients with persistent asthma (ie, patients having symptoms more than twice weekly) receive daily medication for long-term control of asthma.¹ These guidelines consider inhaled corticosteroids the most effective controller medication for persistent asthma.

Recently, leukotriene modifiers have been introduced as a new class of asthma medications. NIH guidelines include leukotriene modifiers as potential alternative controller medications for mild, persistent asthma.¹ However, the guidelines also state that additional data are needed to establish the role and position of leukotriene modifiers in asthma therapy. To date, there have been few published reports of placebo-controlled clinical trials comparing the efficacy, safety, and quality of life in asthma patients treated with an inhaled corticosteroid versus a leukotriene modifier.

This study assessed the clinical benefits of an inhaled corticosteroid and a leukotriene modifier as first-line treatment for persistent asthma in patients who were symptomatic when using short-acting b2-agonists alone.

Methods

Patients

Patients aged 12 years old or older with asthma² were eligible if they had used a short-acting b2-agonist (either scheduled or as-needed) for at least 6 weeks preceding the study, if they had a 1-second forced expiratory volume (FEV₁) between 50% to 80% of predicted values, ^3-5 and if they demonstrated reversibility of FEV₁ (Ž12% increase within 30 minutes after inhaling 180 mg albuterol). Patients were excluded from the study if they had life-threatening asthma, significant and uncontrolled diseases (eg, chronic obstructive pulmonary disease, diabetes, coronary disease), used tobacco products within the preceding year, or had a smoking history of more than 10 pack-years. Patients were also excluded if they received any systemic corticosteroid within 6 months of screening, any inhaled corticosteroid within 1 month of screening, or any leukotriene modifier within 1 week of screening.

Study Design

This randomized double-blind, double-dummy, parallel-group study was conducted at 34 sites in the United States. All patients (or their parent or guardian) gave written informed consent before entering the study. The study was approved by institutional review boards for each site.

Eligible patients entered an 8-to 14-day run-in period to establish baseline respiratory function. Patients who met the study criteria were randomly assigned to receive 1 of the following double-blind, double-dummy treatments every morning and evening for 12 weeks: (1) 88 mg fluticasone propionate (FP [Flovent Inhalation Aerosol], 2 puffs of 44 mg each) administered by metered-dose inhaler (MDI) and a placebo capsule; (2) oral zafirlukast 20 mg (Accolate over-encapsulated tablet) and 2 puffs of placebo by MDI; or (3) a placebo capsule and 2 puffs of placebo by MDI. The zafirlukast dosage (20 mg twice daily) is the currently recommended dosage for patients aged 12 years or older, and 88 mg FP twice daily is the lowest FP dosage delivered by MDI approved for use in adolescents and adults. Treatment assignments were generated by computer in blocks of 6 so that each of the 3 treatments was represented twice in random order.