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

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Cochran-Mantel-Haenszel tests, controlling for investigator, were used to determine treatment differences in physicians’ overall assessment of efficacy (at endpoint), in patient satisfaction with study medication (at week 2 and endpoint), and in the number of patients in each treatment group with at least 1 asthma exacerbation requiring oral or parenteral corticosteroids. Van Elteren tests were used to assess patient productivity.

Results

Patients

A total of 338 patients, 12 to 75 years of age, were randomly assigned to treatment (113, FP; 111, zafirlukast; 114, placebo). Equal numbers of men and women were enrolled in the study, and the majority of patients were non-Hispanic white (86%) or African American (10%). Baseline pulmonary function (% of predicted FEV₁) was similar across treatment groups (66%-67% predicted). The majority of patients in each treatment group had moderate asthma (77%, FP; 82%, zafirlukast; 18%, placebo), and most patients in each treatment group had asthma diagnosed for at least 10 years (64%-73%). A post hoc survey of patients revealed that the majority of respondents (149 of 286 patients; 52%) were recruited from primary care practices for the purpose of the study or were treating their asthma with over-the-counter bronchodilators. Similar numbers of patients in each group completed the study (81%-86% of patients). The most common reasons for discontinuation were lack of efficacy (2%-5%) and withdrawn consent (3%-5%). Median compliance was 93% in each group for both inhaled and oral study medication.

Efficacy

Treatment with FP significantly improved pulmonary function more than zafirlukast or placebo. At the endpoint Table 1 and at individual points as early as day 4 ( Figure 1, mean improvements in FEV₁ and in am PF and pm PEF were significantly greater in the FP group compared with the zafirlukast or placebo group (P <.05). When stratified by baseline pulmonary function (% predicted FEV₁), mean changes in FEV₁ and pm PEF were significantly greater in FP patients than in zafirlukast or placebo patients, regardless of baseline pulmonary function Table 2.

At the endpoint, treatment with FP significantly improved all clinical parameters (mean symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings due to asthma) compared with placebo (P≤.006, Table 1. In contrast, treatment with zafirlukast resulted in significant improvements in albuterol use and the percentage of symptom-free and albuterol-free days (P≤.040, vs placebo), but not in mean symptom scores or the number of nighttime awakenings. Compared with zafirlukast at the endpoint, FP produced significantly greater improvements in mean symptom scores, the percentages of symptom-free and albuterol-free days, albuterol use, and the number of nighttime awakenings due to asthma (P≤.038). When compared with placebo at individual time points, FP produced significantly greater improvements in each clinical parameter at most or all time points (P≤.039). In contrast, treatment with zafirlukast resulted in fewer time points with significantly different improvements in these parameters compared with placebo. Compared with zafirlukast, FP produced significantly greater improvements in mean symptom scores, the percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings due to asthma at the majority of time points from week 2 through week 12 (P≤.050).

At the endpoint, physicians’ overall assessments of study medication efficacy and patients’ overall satisfaction with study medication both significantly favored FP over zafirlukast (P≤.025) or placebo (P <.001; Figure 2. More physicians rated FP “effective” or “very effective” compared with zafirlukast or placebo. Likewise, more FP patients were “satisfied” or “very satisfied” with their study medication than were patients taking zafirlukast or placebo. The patient productivity questionnaire data showed that the mean number of days that patients attended work or school with asthma symptoms was significantly higher in the zafirlukast and placebo groups than the FP group (3.8, 4.4, and 1.8 days, respectively, P≤.03).

At the endpoint, treatment with FP produced significantly greater improvements in global and individual domain AQLQ scores compared with zafirlukast or placebo (P≤.033; Figure 3. Furthermore, treatment differences between FP and placebo for global and most individual domain AQLQ scores are considered clinically meaningful (Ž0.5).⁸ In contrast, zafirlukast did not achieve clinically meaningful differences compared with placebo for any AQLQ endpoint.

Safety

The percentages of patients who experienced at least 1 adverse event were similar across treatment groups (67% to 72%). More FP patients reported sinusitis (12%, vs 4% with zafirlukast and 4% with placebo), and more zafirlukast patients reported chest congestion (5%, vs <1% with FP and 0 with placebo). Oropharyngeal candidiasis was reported for 2 placebo recipients and 3 FP patients. Few patients experienced adverse events potentially related to study medication (12% to 13% of each group). The most common adverse events considered potentially related to study medication were throat irritation (FP: 4% of patients; zafirlukast and placebo: 3% each) and headache (FP: 3%; placebo and zafirlukast: 2% each). Two patients in the FP group and 1 patient in the zafirlukast group and 1 patient in the placebo group discontinued study treatment because of adverse events possibly related to study medication (FP: diarrhea, coughing and hoarseness; zafirlukast: increase in g-glutamyltransferase [GGT; other hepatic enzyme levels were not elevated]; placebo: lightheadedness and shakiness). The only adverse events requiring hospitalization occurred in the placebo group. Few clinically significant laboratory abnormalities ( 3% for any assay) were reported; none were considered related to study medication. Fewer FP patients experienced asthma exacerbations that required treatment with oral corticosteroids compared with zafirlukast or placebo patients (4%, 12%, and 10% of patients, respectively); treatment differences, however, were not statistically significant.