Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (theIMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial)

Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukutrie nes are poorly suppressed by corticosteroids it seems rational to add a leu kotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control. Long acting be ta(2)-agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical be nefits of adding either a LTRA or a LABA to asthma patients inadequately co ntrolled by inhaled corticosteroids, a randomized, double-blind, multi-cent re, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhal ed LABA salmeterol, each administered on a background of inhaled fluticason e, on asthma attacks, quality of life, lung function, eosinophil levels, he althcare utilization, and safety, in approximately 1200 adult asthmatic pat ients. The requirements for study enrolment include a history of asthma, FE V1 or PEFR values between 50% and 90% of the predicted value together with greater than or equal to 12% improvement in FEV1 after beta-agonist adminis tration, a minimum pre-determined level of asthma symptoms and daily beta-a gonist medication. The study will include a 4-week run-in period, during wh ich patients previously taking inhaled corticosteroids are switched to open -label fluticasone (200 mu g daily), followed by a 48-week double-blind, tr eatment period in which patients continuing to experience abnormal pulmonar y function and daytime symptoms are randomized to receive montelukast (10 m g once daily) and salmeterol placebo, or inhaled salmeterol (100 mu g daily ) and montelukast placebo. All patients will continue with inhaled fluticas one (200 mu g daily). During the study, asthma attacks, overnight asthma sy mptoms, and morning peak expiratory flow rate will be assessed using patien t diary cards; quality of life will also be assessed using an asthma-specif ic quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a ra tional and logical treatment choice for asthmatic patients experiencing bre akthrough symptoms on inhaled corticosteroids.