Study Design of VESUTO®: Efficacy of Tiotropium/Olodaterol on Lung Hyperinflation, Exercise Capacity, and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease

Abstract

IntroductionThe superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD.MethodsA protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD.ResultsA total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints.ConclusionThe VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) combination therapy on patients’ physical activities as well as lung function.Trial registrationClinicalTrials.gov: NCT02629965 (registered on December 1, 2015).FundingThe VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0554-3) contains supplementary material, which is available to authorized users.

<p>Effect of tiotropium/olodaterol on sedentary and active time in patients with COPD: post hoc analysis of the VESUTO^® study</p>

“…This was a post hoc analysis of the VESUTO study, where tiotropium/olodaterol combination therapy was compared with tiotropium monotherapy for its ability to improve inspiratory capacity (IC) and physical activity levels in patients with COPD 24. The VESUTO study was a multicenter, randomized, double-blind, active-controlled, two-way crossover trial as described previously 23. All patients received long-acting muscarinic antagonist (LAMA) or long-acting β 2 -agonist (LABA) monotherapy for at least 5 weeks before randomization.…”

“…Tiotropium is a widely used maintenance treatment for COPD. The VESUTO ® study was designed to investigate the efficacy of a fixed dose of tiotropium in combination with olodaterol versus tiotropium monotherapy by assessing lung hyperinflation and exercise capacity in Japanese patients with COPD 23,24. To our knowledge, there are no reports presently available that describe bronchodilator use with reductions in sedentary duration.…”

Efficacy of tiotropium/olodaterol on lung volume, exercise capacity, and physical activity

“…Further details have been described elsewhere. 14 Written informed consent was obtained from all patients prior to the study, which was approved by the institutional review board at each participating center (details of all institutional review boards are provided in Table S1 ).…”

“…Details of the study populations and sample size calculations (Supplementary materials) are given in the published study design paper. 14 …”

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study

“…The VESUTO study16 (Efficacy of tiotropium/olodaterol on lung volume, exercise capacity, and physical activity) set up certain criteria when measuring exercise tolerance and physical activity. That study, as well as ours, will provide important information for evaluating physical activity in patients with COPD in the future.…”