Dual bronchodilation with tiotropium/olodaterol further reduces activity-related breathlessness versus tiotropium alone in COPD

François Maltais, Joseph-Leon Aumann, Anne-Marie Kirsten, Éric Nadreau, Hemani Macesic, Xidong Jin, Alan Hamilton, Denis E O'Donnell, François Maltais, Joseph-Leon Aumann, Anne-Marie Kirsten, Éric Nadreau, Hemani Macesic, Xidong Jin, Alan Hamilton, Denis E O'Donnell

Abstract

The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmonary impairment, lung hyperinflation at rest and a Mahler Baseline Dyspnoea Index <8. Patients received 6 weeks of tiotropium/olodaterol 5/5 µg and tiotropium 5 µg in a randomised order with a 3-week washout period. The speed for the 3-min CSST was determined for each patient such that an intensity of breathing discomfort ≥4 ("somewhat severe") on the modified Borg scale was reached at the end of a completed 3-min CSST.After 6 weeks, there was a decrease in the intensity of breathlessness (Borg dyspnoea score) at the end of the 3-min CSST from baseline with both tiotropium (mean -0.968, 95% CI -1.238- -0.698; n=100) and tiotropium/olodaterol (mean -1.325, 95% CI -1.594- -1.056; n=101). The decrease in breathlessness was statistically significantly greater with tiotropium/olodaterol versus tiotropium (treatment difference -0.357, 95% CI -0.661- -0.053; p=0.0217).Tiotropium/olodaterol reduced activity-related breathlessness more than tiotropium in dyspnoeic patients with moderate to severe COPD exhibiting lung hyperinflation.

Conflict of interest statement

Conflict of interest: F. Maltais reports research support from Boehringer Ingelheim, GSK, AstraZeneca, Grifols and Novartis, advisory board participation for Boehringer Ingelheim and GSK, and speaking engagements for Boehringer Ingelheim, Grifols and Novartis. Conflict of interest: J-L. Aumann has nothing to disclose. Conflict of interest: A-M. Kirsten reports institutional compensation for clinical trials from Boehringer Ingelheim, during the conduct of the study; has lectured for Boehringer Ingelheim, AstraZeneca and Berlin-Chemie, and reports institutional compensation for clinical trials from AstraZeneca, Boehringer Ingelheim, Roche, GSK, Novartis, Chiesi, Bayer Healthcare and Sanofi, outside the submitted work. Conflict of interest: É. Nadreau has nothing to disclose. Conflict of interest: H. Macesic is an employee of Boehringer Ingelheim. Conflict of interest: X. Jin is an employee of Boehringer Ingelheim. Conflict of interest: A. Hamilton is an employee of Boehringer Ingelheim. Conflict of interest: D.E. O'Donnell reports grants from AstraZeneca, Boehringer Ingelheim and GSK, during the conduct of the study; and personal fees for serving on speaker bureaus, consultation panels and advisory boards from Almirall, AstraZeneca, Boehringer Ingelheim, GSK, Novartis and Pfizer, outside the submitted work.

Copyright ©ERS 2019.

Figures

FIGURE 1
FIGURE 1
Trial design. T/O: tiotropium/olodaterol; Tio: tiotropium; ISWT: incremental shuttle walk test; CSST: constant speed shuttle test. #: speed determination; ¶: at visits 4 and 7, a period baseline 3-min CSST was completed prior to dosing; at visits 5, 6, 8 and 9 a 3-min CSST was conducted 2 h (±15 min) after inhalation of the study medication.
FIGURE 2
FIGURE 2
Patient disposition (crossover trial). T/O: tiotropium/olodaterol; Tio: tiotropium; AE: adverse event. #: reasons for exclusion (screen failures) are shown in supplementary table S1; ¶: due to other AE; +: all due to exacerbations.
FIGURE 3
FIGURE 3
Borg dyspnoea score: a) at the end of the 3-min constant speed shuttle test (CSST) (primary end-point) and b) during the 3-min CSST, after 6 weeks of treatment. T/O: tiotropium/olodaterol (n=101); Tio: tiotropium (n=100). Data are presented as mean±se. *: p<0.05 T/O versus Tio.
FIGURE 4
FIGURE 4
Treatment difference in Borg dyspnoea score at 6 weeks: tiotropium/olodaterol (T/O)–tiotropium (Tio). Each individual patient is represented by a single point. Negative scores indicate a larger reduction in Borg dyspnoea score with T/O and positive scores indicate a larger reduction in Borg dyspnoea score with Tio. The dotted lines represent changes in Borg dyspnoea score of 1 unit in both directions. Period baseline was used for this analysis.
FIGURE 5
FIGURE 5
Physiological parameters measured during the 3-min constant speed shuttle test at 6 weeks: a) ventilation, b) tidal volume and c) breathing frequency. T/O: tiotropium/olodaterol (n=101); Tio: tiotropium (n=100). Data are presented as mean±se. *: p<0.05 T/O versus Tio.

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