Tiotropium in patients with moderate COPD naive to maintenance therapy: a randomised placebo-controlled trial

Abstract

Background: The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated. However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).

Aims: To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.

Methods: A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ≥50 and <80%.

Results: A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)). Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs. -0.03 l (least-squares mean difference 0.23 l, P<0.001). FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001). Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS). Physician's Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24. The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.

Conclusions: Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early.

Trial registration: ClinicalTrials.gov NCT00523991.

Figure 1

Study design. V1–V9 Study Visit 1 to 9. V1 and V2 were scheduled 4 and 3 weeks prior to randomisation. HH, HandiHaler.

Figure 2

Patient disposition. ActES, activity evaluable set; FAS, full analysis set.

Figure 3

Lung function outcomes (presented as means±s.e. (a) Pre-dose FEV₁ (raw values in litres) at time −10 min and post-dose FEV₁ at 30, 60, 90, 120, 150 and 180 min, by treatment group at baseline and last study visit; (b) FEV₁ AUC_0–3h; (c) FVC AUC_0–3h; (d) trough FEV₁; and (e) trough FVC by treatment group during the course of the study. AUC_0–3h, area under the curve between 0 and 3 h; CI, confidence interval; FEV₁, forced expiratory volume in 1s; FVC, forced vital capacity; LS, least squares.

Figure 4

Overall physical activity levels (using age-appropriate metabolic equivalents) as shown by (a) mean min/day in moderate- or higher-intensity physical activity and (b) mean number of steps per day in the tiotropium group (solid line) and the placebo group (dashed line).