Effect of 12 weeks of once-daily tiotropium/olodaterol on exercise endurance during constant work-rate cycling and endurance shuttle walking in chronic obstructive pulmonary disease

Abstract

Background: The TORRACTO^® study evaluated the effects of tiotropium/olodaterol versus placebo on endurance time during constant work-rate cycling and constant speed shuttle walking in patients with chronic obstructive pulmonary disease (COPD) after 12 weeks of treatment.

Methods: The effects of once-daily tiotropium/olodaterol (2.5/5 and 5/5 μg) on endurance time during constant work-rate cycle ergometry (CWRCE) after 6 and 12 weeks of treatment were compared with placebo in patients with COPD in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Endurance time during the endurance shuttle walk test (ESWT) after 6 and 12 weeks of treatment was also evaluated in a subset of patients.

Results: A total of 404 patients received treatment, with 165 participating in the ESWT substudy. A statistically significant improvement in endurance time during CWRCE was observed after 12 weeks (primary endpoint) with tiotropium/olodaterol 5/5 µg [14% ( p = 0.02)] but not with tiotropium/olodaterol 2.5/5 µg [9% ( p = 0.14)] versus placebo. In the ESWT substudy, a trend to improvement in endurance time during ESWT after 12 weeks (key secondary endpoint) was observed with tiotropium/olodaterol 5/5 µg [21% ( p = 0.055)] and tiotropium/olodaterol 2.5/5 µg [21% ( p = 0.056)] versus placebo.

Conclusion: Tiotropium/olodaterol 5/5 µg improved endurance time during cycle ergometry versus placebo, with a strong tendency to also improve walking endurance time. [ ClinicalTrials.gov identifier: NCT01525615.].

Keywords: COPD; bronchodilator; constant work-rate cycling; endurance shuttle walking; olodaterol; tiotropium.

Figure 1.

Study design. ^*Cycle ergometry testing; ^$endurance shuttle walk test; ^‡primary endpoint assessment. R, randomization.

Figure 2.

CONSORT diagram. CONSORT, Consolidated Standards of Reporting Trials; O, olodaterol; T, tiotropium.

Figure 3.

Geometric mean exercise endurance time during constant work-rate cycle ergometry after 6 and 12 weeks. ^*Geometric mean results are reported as the primary analysis based on log₁₀-transformed data; week 6 data are not included in hierarchical testing sequence and should be considered descriptive only. Common geometric mean baseline EET: 443.0 s. Placebo, n = 121; T/O 2.5/5 μg, n = 129; T/O 5/5 μg, n = 135. EET, exercise endurance time; O, olodaterol; SE, standard error; T, tiotropium.

Figure 4.

Mean inspiratory capacity (a) and slope of intensity (b) of breathing discomfort after 12 weeks. Mean baseline IC: pre-exercise, 2397 ml; isotime, 2131 ml; end-exercise, 2111 ml. T/O 2.5/5 µg versus placebo, p = 0.0218; T/O 5/5 µg versus placebo, p = 0.0598. IC, inspiratory capacity; O, olodaterol; SE, standard error; T, tiotropium.

Figure 5.

Geometric mean endurance shuttle walk test endurance time after 6 and 12 weeks in the endurance shuttle walk test subgroup. ^*Geometric mean results reported as primary analysis based on log₁₀-transformed data; week 6 data are not included in hierarchical testing sequence and should be considered descriptive only. Common geometric mean baseline ESWT endurance time: 311.2 s. Placebo, n = 50; T/O 2.5/5 μg, n = 56; T/O 5/5 μg, n = 59. ESWT, endurance shuttle walk test; O, olodaterol; SE, standard error; T, tiotropium.