NCT identifier and citation(s) | Study design | COPD inclusion criteria | Baseline lung function values | Patient numbers and treatment groups | Endpoints |
---|---|---|---|---|---|
Primary tiotropium trial publications | |||||
NCT02175342 Caillaud D, et al. Int J Chron Obstruct Pulmon Dis. 2007;2:559–65 [26] | Multicentre, randomized, double-blind within device (no blinding between RMT and HH), parallel-group, 3-week dose-ranging Phase II study | FEV1/FVC ≤70% FEV1 30–65% predicted Smoking history ≥10 pack-years | Mean FEV1 44% predicted | n = 202 RMT 5 μg (n = 25) HH 18 μg (n = 25) | Efficacy 1o: mean change in trough FEV1 from baseline to Day 21 2o: FVC and rescue medication use |
NCT01222533 Hohlfeld JM, et al. J Clin Pharmacol. 2014;54:405–14 [31] | Comparative, multicentre, placebo-controlled, randomized (double-blind within RMT 1.25, 2.5, 5 μg; open-label HH 18 μg), 5-way crossover trial with 4-week treatment periods | FEV1/FVC <70% FEV1 < 80% predicted | FEV1/FVC 45% Mean FEV1 54% predicted | n = 154 RMT 5 μg (n = 150) HH 18 μg (n = 146) | Efficacy 1o: trough FEV1 at end of 24-h dosing interval 2o: FVC, peak expiratory flow and rescue medication use |
NCT00292448 Ichinose M, et al. Respir Med. 2010;104:228–36 [33] | Randomized, double-blind, double-dummy, 2-way, 4-week crossover, Phase II study of Japanese patients with COPD | FEV1/FVC ≤70% FEV1 ≤ 70% predicted Current or ex-smokers | FEV1/FVC 42% Mean FEV1 43% predicted | n = 157 RMT 5 μg (n = 147) HH 18 μg (n = 147) | Efficacy 1o: trough FEV1 response 2o: peak and average FEV1 and FVC |
NCT00239447 and NCT00281567 van Noord JA, et al. Respir Med. 2009;103:22–9 [37] | Pre-specified, pooled analysis of two identical, 30-week, double-blind, double-dummy, crossover studies (4-week crossover periods) | FEV1/FVC ≤70% FEV1 ≤ 60% predicted | Mean FEV1 37% predicted | n = 207 Included in efficacy and safety analyses: RMT 5 μg (n = 189) HH 18 μg (n = 189) | Efficacy 1o: trough FEV1 from baseline to Day 29 2o: trough and peak FVC, FVC AUC(0-12h), peak FEV1 and FEV1 AUC(0-12h) at Day 29, and the time to therapeutic response |
TIOSPIR® 205.452/NCT01126437 Wise RA, et al. N Engl J Med. 2013;369:1491–501 [48] | Randomized, double-blind, double-dummy, parallel-group, event-driven trial, duration 2–3 years | FEV1/FVC ≤70% FEV1 ≤ 70% predicted | Mean post-bronchodilator FEV1 48% predicted for total population | n = 17,135 At risk, mortality RMT 5 μg (n = 5711) RMT 2.5 μg (n = 5730) HH 18 μg (n = 5694) At risk, exacerbation RMT 5 μg (n = 5705) RMT 2.5 μg (n = 5724) HH 18 μg (n = 5687) | Safety 1o: time to all-cause mortality Efficacy 1o: time to first COPD exacerbation Secondary outcomes: number of exacerbations; time to the first MACE |
TIOSPIR® 205.452/NCT01126437 Anzueto A, et al. Respir Res. 2015;16:107 [24] | Spirometry sub-study Randomized, double-blind, double-dummy, parallel-group, event-driven trial, duration 2–3 years | FEV1/FVC ≤70% FEV1 ≤ 70% predicted | Mean post-bronchodilator FEV1 48% predicted for total population | n = 1370 RMT 5 μg (n = 461) HH 18 μg (n = 445) | Trough FEV1 and FVC |
Randomized parallel-group trial | Mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake) | NR | n = 200 randomized RMT (n =100) HH (n =100 Patients analysed: RMT (n = 95) HH (n = 93) | SaO2 and sleep quality | |
Pooled, combined and database analyses | |||||
Tashkin D, et al. Chest. 2014;146 r_Meeting Abstracts:49A [34] | 16 clinical trials (13 tiotropium HandiHaler®, 3 tiotropium Respimat®) | Moderate to very severe COPD | NR | HH 18 μg (13 trials, n = 5646) Active comparator (2 trials, n = 584) Placebo (11 trials, n = 4853) RMT 5 μg (3 trials, n = 2219) RMT 10 μg (2 trials, n = 619) Placebo (3 trials, n = 2318) | HRQoL evaluated using the SGRQ |
Dahl R, et al. Eur Respir J. 2014;44 Suppl 58:925 [28] | Post-hoc, pooled analysis of all placebo-controlled or head-to-head trials of RMT 5 μg and HH 18 μg with vital status follow up (analysed for death) and those with duration of at least 1 year (analysed for exacerbations) | COPD | NR | At risk of mortality, 6 trials: RMT 5 μg (n = 8760) HH 18 μg (n = 8680) Placebo (n = 6053) At risk of exacerbations, 5 trials: RMT 5 μg (n = 8314) HH 18 μg (n = 8673) Placebo (n = 5612) | Number of deaths Number of patients with ≥1 exacerbation |
Halpin DMG, et al. Int J Chron Obstruct Pulmon Dis. 2015;10:239–59 [30] | Pooled analysis of adverse event data from 28 HH and 7 RMT studies | FEV1 ≤ 70% of FVC | Mean FEV1 41% predicted | Patients treated: RMT 5 μg (n = 3282) RMT placebo (n = 3283) HH 18 μg (n = 9647) HH placebo (n = 8343) | Safety: AEs |
Hohlfeld JM, et al. Int J Clin Pract. 2015;69:72–80 [32] | Combined analysis of all tiotropium trials in COPD involving Holter ECG monitoring and conducted between 2003 and 2012 | FEV1 ≤ 70% of FVC | NR | 4 trials (n = 727) HH 18 μg RMT 1.25–10 μg | Safety: incidence of cardiac arrhythmias |
Tashkin D, et al. Eur Respir J. 2014;44 Suppl 58:923 [35] | Safety analysis in patients with renal impairment included in placebo-controlled trials of once-daily tiotropium Respimat® 5 μg (7 trials) or tiotropium HandiHaler® 18 μg (15 trials) | COPD and renal impairment | NR | n = 10,753 evaluable patients Normal renal function, mild and moderate renal impairment (respectively): HH 18 μg (n = 860), (n = 1099), (n = 448) HH placebo (n = 700), (n = 815), (n = 347) RMT 5 μg (n = 1104), (n = 1479), (n = 662) RMT placebo (n = 1040), (n = 1539), (n = 660) | Safety: AEs |
Verhamme K, et al. Eur Respir J. 2013; 42 Suppl 57:4632 [38] Verhamme KM, et al. Eur Respir J. 2013;42: 606–15 [39] | Study of Integrated Primary Care Information Database (large Dutch primary care database) | COPD | NR | n = 11,287 (24,522 episodes of tiotropium use) | Safety: comorbidity |