The prevention of COPD exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.

Rationale: Exacerbations are key drivers of morbidity and mortality in chronicobstructive pulmonary disease (COPD).Objectives: We compared the relative efficacy of the long-acting inhaledbronchodilator/anti-inflammatory combination (salmeterol/fluticasone propionate) 50/500mcg bd and the long-acting bronchodilator (tiotropium) 18mcg od in preventing exacerbations and related outcomes in moderate severe COPD Methods: 1323 patients (mean age 64yr, forced expiratory volume in 1sec 39 per cent predicted) were randomized in 2-year, double blind, double-dummy, parallel study.Measurements and Main Results: Primary endpoint was healthcare utilization exacerbation rate. Other endpoints included health status measured by St. Georges Respiratory Questionnaire (SGRQ), mortality, adverse events and study withdrawal.Probability of withdrawing from the study was 29 per cent greater with tiotropium than salmeterol/fluticasone propionate (p=0.005). The modelled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio 0.967 [95 per cent CI: 0.836 to 1.119]; p=0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionateversus tiotropium (difference 2.1 units, 95 per cent CI: 0.1 to 4.0, p=0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3 per cent of patients in this group died compared to 38 (6 per cent) in the tiotropium group (p=0.032). Morepneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (p=0.008).Conclusions: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate treated patients.

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.