Trial [ref.] | Asthma severity | Key trial background medication | Key spirometric entry criteria | Treatment arm | Adjusted mean difference in response compared with placebo | ||||
ICS dose# µg | LABA | Peak FEV1 mL | Trough FEV1 mL | Morning PEF L·min−1 | Evening PEF L·min−1 | ||||
NCT00365560¶ [54] | Severe | ≥800 | Yes | ≤80% of predicted post-BD FEV1 FEV1 ≤70% of FVC | Tiotropium 10 µg once daily | 170 (p<0.001, n=103) | 113 (p<0.002, n=103) | 15.3 (p<0.001, n=103) | 23.3 (p<0.001, n=103) |
Tiotropium 5 µg once daily | 139 (p<0.001, n=104) | 86 (p<0.001, n=104) | 7.9 (p=0.02, n=104) | 14.7 (p<0.001, n=104) | |||||
NCT00350207+ [55] | Moderate | 400–1000 | No | ≤90% of predicted pre-BD FEV1 | Tiotropium 5 µg once daily | ND | 149## (p<0.001, n=128) | 20.7 (p=0.001, n=128) | 23.6 (p=0.001, n=128) |
Salmeterol 50 µg twice daily | ND | 167 (p<0.001, n=134) | 21.5 (p=0.001, n=134) | 20.2 (p=0.001, n=134) | |||||
NCT01233284+ [56] | Moderate | 400–800 | No | 60–90% of predicted pre-BD FEV1 | Tiotropium 5 µg once daily | 188 (p<0.001, n=143) | 143 (p<0.001, n=143) | 20.8 (p<0.0001, n=143) | 21.6 (p<0.0001, n=143) |
Tiotropium 2.5 µg once daily | 128 (p<0.001, n=144) | 132 (p<0.001, n=144) | 17.9 (p<0.0001, n=144) | 14.6 (p<0.0001, n=144) | |||||
Tiotropium 1.25 µg once daily | 139 (p<0.001, n=144) | 125 (p<0.001, n=144) | 18.6 (p<0.0001, n=144) | 21.3 (p<0.0001, n=144) | |||||
NCT01152450+ [57] | Moderate | 400–800 | No | 60–90% of predicted pre-BD FEV1 | Tiotropium 5 µg once daily | 131 (p<0.01, n=90) | 133 (p<0.01, n=90) | 22 (p<0.01, n=88) | 29 (p<0.01, n=89) |
Tiotropium 2.5 µg twice daily | 132 (p<0.01, n=89) | 111 (p<0.01, n=89) | 21 (p<0.01, n=89) | 30 (p<0.01, n=89) | |||||
NCT00772538, NCT00776984§ [58] | Severe | ≥800 | Yes | ≤80% of predicted post-BD FEV1 FEV1 ≤70% of FVC | Tiotropium 5 µg once daily | 110 (p<0.0001, n=422) | 93 (p<0.0001, n=421) | 22.6 (p<0.0001, n=411) | 26.4 (p<0.0001, n=408) |
NCT01172808, NCT01172821ƒ [59] | Moderate | 400–800 | No | 60–90% of predicted pre-BD FEV1 | Tiotropium 5 µg once daily | 185 (p<0.0001, n=481) | 146 (p<0.0001, n=481) | 24.3 (p<0.0001, n=472) | 23.2 (p<0.0001, n=472) |
Tiotropium 2.5 µg once daily | 223 (p<0.0001, n=492) | 180 (p<0.0001, n=492) | 25.4 (p<0.0001, n=485) | 22.1 (p<0.0001, n=483) | |||||
Salmeterol 50 µg twice daily | 196 (p<0.0001, n=510) | 114 (p<0.0001, n=510) | 24.8 (p<0.0001, n=501) | 20.7 (p<0.0001, n=499) |
All analyses performed on the full analysis set. ICS: inhaled corticosteroids; LABA: long-acting β2-agonist; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; PEF: peak expiratory flow; BD: bronchodilator (salbutamol); ND: not defined. #: budesonide or equivalent; ¶: phase II study in adults with severe asthma; +: phase II study in adults with moderate asthma; §: phase III study in adults with severe asthma; ƒ: phase III study in adults with moderate asthma; ##: defined as morning pre-dose FEV1.