Table 9.
IRs (per 100 patient-years) and RRs for FAEs according to SOC and PTa
| HandiHaler®
|
Respimat®
|
Total
|
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placebo n=8,343 |
Tiotropium n=9,647 |
RR (95% CI) | Placebo n=3,283 |
Tiotropium n=3,282 |
RR (95% CI) | Placebo n=11,626 |
Tiotropium n=12,929 |
RR (95% CI) | |||||||
| n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | n (%) | IR | ||||
| Respiratory, thoracic, and mediastinal disorders | 143 (1.7) | 1.23 | 118 (1.2) | 0.90 | 0.74 (0.58, 0.95)b | 16 (0.5) | 0.62 | 16 (0.5) | 0.59 | 0.96 (0.48, 1.92) | 159 (1.4) | 1.12 | 134 (1.0) | 0.84 | 0.76 (0.61, 0.96)b |
| COPD | 67 (0.8) | 0.57 | 61 (0.6) | 0.46 | 0.82 (0.58, 1.16) | 4 (0.1) | 0.16 | 8 (0.2) | 0.30 | 1.88 (0.56, 6.28) | 71 (0.6) | 0.50 | 69 (0.5) | 0.43 | 0.88 (0.63, 1.22) |
| Respiratory failure | 51 (0.6) | 0.44 | 33 (0.3) | 0.25 | 0.59 (0.38, 0.91)b | 5 (0.2) | 0.19 | 2 (0.1) | 0.07 | 0.37 (0.07, 1.99) | 56 (0.5) | 0.39 | 35 (0.3) | 0.22 | 0.57 (0.37, 0.87)b |
| Acute respiratory failure | 8 (0.1) | 0.07 | 8 (0.1) | 0.06 | 0.92 (0.35, 2.46) | 2 (0.1) | 0.08 | 0 (0.0) | 0.00 | 0 | 10 (0.1) | 0.07 | 8 (0.1) | 0.05 | 0.74 (0.29, 1.89) |
| Neoplasms benign, malignant, and unspecified | 118 (1.4) | 1.01 | 117 (1.2) | 0.89 | 0.91 (0.70, 1.17) | 5 (0.2) | 0.19 | 8 (0.2) | 0.30 | 1.53 (0.50, 4.68) | 123 (1.1) | 0.87 | 125 (1.0) | 0.79 | 0.93 (0.73, 1.20) |
| Lung neoplasm malignant | 19 (0.2) | 0.16 | 21 (0.2) | 0.16 | 1.00 (0.54, 1.85) | 2 (0.1) | 0.08 | 4 (0.1) | 0.15 | 1.92 (0.35, 10.59) | 21 (0.2) | 0.15 | 25 (0.2) | 0.16 | 1.09 (0.61, 1.93) |
| Cardiac disorders | 106 (1.3) | 0.91 | 89 (0.9) | 0.67 | 0.75 (0.56, 0.99)b | 12 (0.4) | 0.47 | 23 (0.7) | 0.85 | 1.86 (0.92, 3.75) | 118 (1.0) | 0.83 | 112 (0.9) | 0.70 | 0.80 (0.66, 1.11) |
| Cardiac failure | 10 (0.1) | 0.09 | 14 (0.1) | 0.11 | 1.25 (0.55, 2.83) | 4 (0.1) | 0.16 | 2 (0.1) | 0.07 | 0.47 (0.08, 2.66) | 14 (0.1) | 0.10 | 16 (0.1) | 0.10 | 1.04 (0.50, 2.14) |
| MI and acute MI | 25 (0.3) | 0.21 | 20 (0.2) | 0.15 | 0.71 (0.39,1.30) | 3 (0.1) | 0.12 | 6 (0.2) | 0.22 | 1.94 (0.48, 7.81) | 28 (0.2) | 0.20 | 26 (0.2) | 0.16 | 0.84 (0.49, 1.45) |
| Cardiac arrest | 17 (0.2) | 0.15 | 10 (0.1) | 0.08 | 0.53 (0.24,1.17) | 2 (0.1) | 0.08 | 2 (0.1) | 0.07 | 0.98 (0.14, 6.90) | 19 (0.2) | 0.13 | 12 (0.1) | 0.08 | 0.58 (0.28, 1.20) |
| Cardiopulmonary failure | 8 (0.1) | 0.07 | 9 (0.1) | 0.07 | 1.00 (0.38, 2.63) | 2 (0.1) | 0.08 | 1 (0.0) | 0.04 | 0.49 (0.04, 5.36) | 10 (0.1) | 0.07 | 10 (0.1) | 0.06 | 0.90 (0.37, 2.19) |
| Cardiorespiratory arrest | 6 (0.1) | 0.05 | 7 (0.1) | 0.05 | 1.09 (0.37, 3.23) | 1 (0.0) | 0.04 | 4 (0.1) | 0.15 | 3.92 (0.44, 35.09) | 7 (0.1) | 0.05 | 11 (0.1) | 0.07 | 1.49 (0.58, 3.81) |
| Cardiac failure congestive | 10 (0.1) | 0.09 | 6 (0.1) | 0.05 | 0.51 (0.18, 1.45) | 0 (0.0) | 0.00 | 1 (0.0) | 0.04 | 10 (0.1) | 0.07 | 7 (0.1) | 0.04 | 0.60 (0.22, 1.63) | |
| Infections and infestations | 63 (0.8) | 0.54 | 61 (0.6) | 0.46 | 0.88 (0.62, 1.26) | 9 (0.3) | 0.35 | 7 (0.2) | 0.26 | 0.75 (0.28, 2.04) | 72 (0.6) | 0.51 | 68 (0.5) | 0.43 | 0.87 (0.62, 1.21) |
| Pneumonia | 26 (0.3) | 0.22 | 26 (0.3) | 0.20 | 0.91 (0.53, 1.57) | 3 (0.1) | 0.12 | 2 (0.1) | 0.07 | 0.63 (0.10, 3.90) | 29 (0.2) | 0.20 | 28 (0.2) | 0.18 | 0.89 (0.53, 1.49) |
| Sepsis | 17 (0.2) | 0.15 | 8 (0.1) | 0.06 | 0.44 (0.19, 1.01) | 1 (0.0) | 0.04 | 0 (0.0) | 0.00 | 0 | 18 (0.2) | 0.13 | 8 (0.1) | 0.05 | 0.41 (0.18, 0.95)b |
| Septic shock | 8 (0.1) | 0.07 | 6 (0.1) | 0.05 | 0.69 (0.24, 2.00) | 3 (0.1) | 0.12 | 1 (0.0) | 0.04 | 0.33 (0.03, 3.12) | 11 (0.1) | 0.08 | 7 (0.1) | 0.04 | 0.59 (0.23, 1.54) |
| General disorders and administration site conditions | 55 (0.7) | 0.47 | 60 (0.6) | 0.45 | 1.00 (0.69, 1.44) | 4 (0.1) | 0.16 | 10 (0.3) | 0.37 | 2.38 (0.76, 7.43) | 59 (0.5) | 0.41 | 70 (0.5) | 0.44 | 1.09 (0.77, 1.54) |
| Death | 28 (0.3) | 0.24 | 37 (0.4) | 0.28 | 1.20 (0.73, 1.97) | 3 (0.1) | 0.12 | 5 (0.2) | 0.18 | 1.57 (0.39, 6.36) | 31 (0.3) | 0.22 | 42 (0.3) | 0.26 | 1.24 (0.78, 1.97) |
| Sudden death | 11 (0.1) | 0.09 | 12 (0.1) | 0.09 | 1.00 (0.44, 2.27) | 1 (0.0) | 0.04 | 2 (0.1) | 0.07 | 1.96 (0.18, 21.63) | 12 (0.1) | 0.08 | 14 (0.1) | 0.09 | 1.08 (0.50, 2.33) |
| Nervous system disorders | 16 (0.2) | 0.14 | 18 (0.2) | 0.14 | 1.02 (0.52, 2.01) | 1 (0.0) | 0.04 | 1 (0.0) | 0.04 | 0.92 (0.06, 13.48) | 17 (0.1) | 0.12 | 19 (0.1) | 0.12 | 1.02 (0.53, 1.96) |
| Vascular disorders | 17 (0.2) | 0.15 | 8 (0.1) | 0.06 | 0.44 (0.19, 1.02) | 1 (0.0) | 0.04 | 0 (0.0) | 0.00 | 0 | 18 (0.2) | 0.13 | 8 (0.1) | 0.05 | 0.42 (0.18, 0.96)b |
| Renal and urinary disorders | 1 (0.0) | 0.01 | 6 (0.1) | 0.05 | 5.75 (0.67, 49.16) | 0 (0.0) | 0.00 | 2 (0.1) | 0.07 | 1 (0.0) | 0.01 | 8 (0.1) | 0.05 | 7.65 (0.93, 63.05) | |
Notes:
a
SOCs with a frequency of at least 3% of the total number of fatal events within any of the treatment arms in either study pool, ie, HandiHaler®, Respimat® or both combined are shown; PTs with an occurrence of at least 10 fatal events within the pooled analysis are shown.
b
Significantly different from 1.
Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FAE, fatal adverse event; IR, incidence rate; MI, myocardial infarction; PT, preferred term; RR, rate ratio; SOC, system organ class.