A randomized trial of symptom-based management in Japanese patients with COPD.

Background: The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations. This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a randomized controlled clinical trial setting. Methods: Japanese patients with moderate-to-severe COPD were randomized to blinded, double-dummy treatment with twice-daily fluticasone propionate/salmeterol (FP/SAL) 250/50 µg or once-daily tiotropium bromide (TIO) 18 µg for 24 weeks (dual bronchodilator was not available). At 4-weekly intervals, patients remaining symptomatic (COPD Assessment Test score >10) or experiencing an exacerbation were offered the option to use triple therapy. Primary endpoint was the proportion of patients remaining on randomized therapy. Results: In total, 406 patients participated (mean FEV1 59%±13% predicted; COPD Assessment Test 12±6). Of these, 204 and 201 patients were included in the FP/SAL and TIO groups, respectively, of whom 67% and 63% continued treatment throughout the study; this difference was not statistically significant. Time to first therapy switch was longer with FP/SAL, but not significantly (P=0.21). More patients in Global initiative for chronic Obstructive Lung Disease (2011 criteria) groups C/D switched (FP/SAL 55%, TIO 63%) than in groups A/B (FP/SAL 27%, TIO 27%). Conclusion: Given the choice, patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy. Effectiveness of disease management pathways can be tested using double-blind studies.

Triple therapy with salmeterol/fluticasone propionate 50/250 plus tiotropium bromide improve lung function versus individual treatments in moderate-to-severe Japanese COPD patients: a randomized controlled trial - Evaluation of Airway sGaw after treatment with tripLE.

PURPOSE: Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 µg (SFC250) twice daily plus tiotropium 18 µg (TIO) once daily and individual treatments on lung function were compared. PATIENTS AND METHODS: Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry. RESULTS: The primary endpoint of postdose specific airway conductance area under the curve (AUC0-4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008). SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28. Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume. There was no mean change seen in rescue medication. CONCLUSION: Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD. There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use.