Investigating new standards for prophylaxis in reduction of exacerbations--the INSPIRE study methodology.

Bronchodilators, including long-acting beta(2)-adrenoceptor agonists and anticholinergic bronchodilators, are effective in the treatment of chronic obstructive pulmonary disease. Evidence suggests that the addition of a long-acting beta(2)-agonist to an inhaled corticosteroid is associated with a reduced rate of exacerbations compared with either treatment alone or placebo. However, it is not known whether a long-acting beta(2)-agonist/inhaled corticosteroid combination is more effective than an anticholinergic bronchodilator alone in reducing exacerbations. The Investigating New Standards for Prophylaxis In Reduction of Exacerbations (INSPIRE) trial will study salmeterol (a long-acting beta(2)-agonist) in combination with fluticasone propionate (an inhaled corticosteroid) compared with tiotropium bromide (an anticholinergic bronchodilator) in patients with moderate-to-severe chronic obstructive pulmonary disease. The INSPIRE study is a multicentre, randomised, double-blind, double dummy, parallel group study conducted over 104 weeks. This is the first study to use two parallel definitions of an exacerbation; an event-based exacerbation is defined as one that requires use of healthcare resources, including additional treatment and hospitalization, whereas a symptom-based exacerbation is defined as one that satisfies the 1987 Anthonisen criteria. It is also the first study to compare the long-term effects of salmeterol/fluticasone propionate with tiotropium bromide on the rate of event-based exacerbations. Endpoints include rate of exacerbations (primary endpoint), time to first exacerbation, and duration of exacerbations. Health outcomes will be assessed via the St George's Respiratory Questionnaire. If the innovative methodology of utilizing 2 definitions of exacerbation proves successful, it will set the benchmark for future studies in chronic obstructive pulmonary disease.