Effects of combined tiotropium/olodaterol on inspiratory capacity and exercise endurance in COPD

Denis E O'Donnell, Richard Casaburi, Peter Frith, Anne Kirsten, Dorothy De Sousa, Alan Hamilton, Wenqiong Xue, François Maltais, Denis E O'Donnell, Richard Casaburi, Peter Frith, Anne Kirsten, Dorothy De Sousa, Alan Hamilton, Wenqiong Xue, François Maltais

Abstract

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2, respectively. Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001). Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies. Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.

Trial registration: ClinicalTrials.gov NCT01533935 NCT01533922.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com

Copyright ©ERS 2017.

Figures

FIGURE 1
FIGURE 1
Study design. O: olodaterol; T: tiotropium; CWRCE: constant work-rate cycle ergometry; IC: inspiratory capacity; EET: exercise endurance time. Incomplete-crossover study: four of five treatments given once daily in random order (placebo, O 5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg), all via the Respimat inhaler.
FIGURE 2
FIGURE 2
Participant flow (combined studies). O: olodaterol; T: tiotropium; IC: inspiratory capacity; EET: exercise endurance time. As these were incomplete-crossover studies, patients received four out of five possible treatments.
FIGURE 3
FIGURE 3
Adjusted mean±se inspiratory capacity (IC) pre-exercise, at isotime and at end-exercise after 6 weeks (combined studies). O: olodaterol; T: tiotropium. As each patient only received four out of five possible treatments, isotimes differ between treatments.
FIGURE 4
FIGURE 4
Adjusted geometric mean±se exercise endurance time (EET) during constant work-rate cycle ergometry after 6 weeks of treatment (combined studies). O: olodaterol; T: tiotropium. *: p<0.05; **: p<0.01; ***: p<0.0001.
FIGURE 5
FIGURE 5
Adjusted mean±se intensity of breathing discomfort (Borg scale) after 6 weeks at pre-exercise, isotime and end-exercise (combined studies). O: olodaterol; T: tiotropium. NS: nonsignificant.

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