Effect of Once-Daily Tiotropium and Olodaterol, Alone and Combined With Exercise Training, on Two Measures of Walking Capacity in Patients With COPD

Abstract

SESSION TITLE: Airways 3 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: PHYSACTO® (NCT02085161) tested effects of bronchodilators alone or with exercise training (ExT), combined with a physical activity behavior-modification (BM) program, on walking capacity in COPD patients. We assessed effects on two walking tests; the endurance shuttle-walk test (ESWT), where walking speed is externally paced, and the 6 minute walk test (6MWT), a self-paced test. METHODS: In this 12-week (wk), randomized, partially double-blind, placebo (P)-controlled, parallel-group trial, interventions (all + 12-wk BM) were P, tiotropium (T) 5 µg, T + olodaterol (T+O) 5/5 µg, and T+O 5/5 µg with 8-wk ExT (T+O 5/5 µg + ExT). Primary endpoint was exercise endurance time (EET) to symptom limitation during ESWT after 8 wks. A further endpoint was 6MWT distance after 8 wks. For both ESWT and 6MWT, intensity of breathing discomfort (BrD) and leg discomfort (LeD) were measured pre-exercise, every 2 min during, and at end-exercise (modified Borg scale). RESULTS: 304 patients were randomized, 303 treated [full analysis set (FAS) n=274]. Baseline geometric mean (SE) EET during ESWT (FAS) was 242.7 (9.4) seconds (s), with a mean (SE) end-exercise BrD of 5.1 (0.1) Borg units (B) (“severe”) and mean (SE) end-exercise LeD of 3.7 (0.2) B (“moderate” / “somewhat severe”); baseline mean (SE) 6MWT distance was 456.9 (5.9) m, with a mean (SE) end-exercise BrD of 3.1 (0.1) B (“moderate”) and mean (SE) end-exercise LeD of 2.4 (0.1) B (“slight” / “moderate”). Adjusted geometric mean (SE) EET during ESWT at 8 wks was 244.1 (17.7) s for P, 254.2 (18.1) s for T 5 µg, 315.3 (21.7) s for T+O 5/5 µg, and 355.7 (24.8) s for T+O 5/5 µg + ExT. EET significantly increased with T+O 5/5 µg (29%; p=0.0109) and T+O 5/5 µg + ExT (46%; p=0.0002) versus P. Adjusted mean (SE) distance during 6MWT after 8 wks was 463.6 (7.4) m for P, 459.0 (7.1) m for T 5 µg, 484.6 (6.6) m for T+O 5/5 µg, and 490.9 (6.9) m for T+O 5/5 µg + ExT. Distance was improved with T+O 5/5 µg [21.0 m (5%); p=0.0344] and T+O 5/5 µg + ExT [27.3 m (6%); p=0.0070] versus P. CONCLUSIONS: After 8 wks, T+O 5/5 µg, alone and combined with ExT, improved EET during ESWT and 6MWT distance compared to P in moderate to severe COPD. The magnitude of improvement was greater for the ESWT than for the 6MWT. CLINICAL IMPLICATIONS: The externally paced ESWT is more responsive to pharmacological and non-pharmacological treatment than the self-paced 6MWT. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion. DISCLOSURE: François Maltais: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Novartis, Other: Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Nycomed, Novartis Alan Hamilton: Employee: Boehringer-Ingelheim Matthias Trampisch: Employee: Boehringer-Ingelheim Carlos Tafur: Employee: Boehringer-Ingelheim Thierry Troosters: Grant monies (from industry related sources): IMI-JU Grant number #115011, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, GSK, Fees paid to Institution No Product/Research Disclosure Information