Trial Outcomes & Findings for Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Moderate Persistent Asthma (NCT NCT01634139)
NCT ID: NCT01634139
Last Updated: 2016-07-12
Results Overview
Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
COMPLETED
PHASE3
403 participants
Baseline and 24 Weeks.
2016-07-12
Participant Flow
Participant milestones
| Measure |
Placebo Respimat
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Overall Study
STARTED
|
132
|
136
|
135
|
|
Overall Study
COMPLETED
|
122
|
130
|
130
|
|
Overall Study
NOT COMPLETED
|
10
|
6
|
5
|
Reasons for withdrawal
| Measure |
Placebo Respimat
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Overall Study
Non compliant with protocol
|
1
|
0
|
0
|
|
Overall Study
Consent withdrawn not due to AE
|
4
|
3
|
2
|
|
Overall Study
Other
|
4
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
0
|
|
Overall Study
Not treated
|
1
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Moderate Persistent Asthma
Baseline characteristics by cohort
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Total
n=401 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
9.0 Years
STANDARD_DEVIATION 1.6 • n=5 Participants
|
9.0 Years
STANDARD_DEVIATION 1.6 • n=7 Participants
|
8.9 Years
STANDARD_DEVIATION 1.7 • n=5 Participants
|
8.9 Years
STANDARD_DEVIATION 1.6 • n=4 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
137 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
85 Participants
n=5 Participants
|
97 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
264 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 24 Weeks.Population: Full Analysis Set (FAS) was equal to treated set which included all randomised patients who received at least 1 documented dose of study medication. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Outcome measures
| Measure |
Placebo Respimat
n=126 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=131 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=134 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 Peak (0-3h) Change From Baseline
|
0.225 Litres (L)
Standard Error 0.027
|
0.395 Litres (L)
Standard Error 0.026
|
0.389 Litres (L)
Standard Error 0.026
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: Full Analysis Set (FAS) was equal to treated set which included all randomised patients who received at least 1 documented dose of study medication. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from Baseline in Trough (pre-dose) Forced Expiratory Volume (FEV) in 1 second (FEV1) measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Trough FEV1 Change From Baseline
Week 24 (N=126, 131, 134)
|
0.156 Litres (L)
Standard Error 0.031
|
0.272 Litres (L)
Standard Error 0.030
|
0.274 Litres (L)
Standard Error 0.030
|
|
Trough FEV1 Change From Baseline
Week 48 (N=124, 130, 130)
|
0.266 Litres (L)
Standard Error 0.032
|
0.337 Litres (L)
Standard Error 0.030
|
0.365 Litres (L)
Standard Error 0.031
|
SECONDARY outcome
Timeframe: Baseline and Week 48.Population: FAS. Missing data at a visit was imputed by available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Outcome measures
| Measure |
Placebo Respimat
n=124 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=130 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=130 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 Peak (0-3h) at Week 48 Change From Baseline
|
0.351 Litres (L)
Standard Error 0.027
|
0.474 Litres (L)
Standard Error 0.026
|
0.477 Litres (L)
Standard Error 0.026
|
SECONDARY outcome
Timeframe: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at week 24Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline of area under the curve (AUC) from 0 to 3 hours for FEV1 (FEV1 AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Outcome measures
| Measure |
Placebo Respimat
n=126 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=131 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=134 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 AUC (0-3h) Change From Baseline
|
0.152 Litres (L)
Standard Error 0.026
|
0.306 Litres (L)
Standard Error 0.025
|
0.309 Litres (L)
Standard Error 0.025
|
SECONDARY outcome
Timeframe: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeksPopulation: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
FEV1 change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 Change From Baseline at Each Individual Timepoint
10 minutes pre-dose (Week 24) (N=126, 131, 134)
|
0.156 Litres (L)
Standard Error 0.031
|
0.272 Litres (L)
Standard Error 0.030
|
0.274 Litres (L)
Standard Error 0.030
|
|
FEV1 Change From Baseline at Each Individual Timepoint
30 minutes post-dose (Week 24) (N=126, 131, 134)
|
0.156 Litres (L)
Standard Error 0.027
|
0.295 Litres (L)
Standard Error 0.026
|
0.307 Litres (L)
Standard Error 0.027
|
|
FEV1 Change From Baseline at Each Individual Timepoint
1 hour post-dose (Week 24) (N=126, 131, 134)
|
0.165 Litres (L)
Standard Error 0.028
|
0.313 Litres (L)
Standard Error 0.027
|
0.312 Litres (L)
Standard Error 0.027
|
|
FEV1 Change From Baseline at Each Individual Timepoint
2 hours post-dose (Week 24) (N=126, 131, 134)
|
0.144 Litres (L)
Standard Error 0.028
|
0.307 Litres (L)
Standard Error 0.027
|
0.312 Litres (L)
Standard Error 0.027
|
|
FEV1 Change From Baseline at Each Individual Timepoint
3 hours post-dose (Week 24) (N=126, 131, 134)
|
0.147 Litres (L)
Standard Error 0.027
|
0.325 Litres (L)
Standard Error 0.026
|
0.322 Litres (L)
Standard Error 0.026
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 24 and 48 Weeks of treatment. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FVC Peak(0-3h) Change From Baseline
Week 24 (N=124, 130, 134)
|
0.215 Litres (L)
Standard Error 0.033
|
0.325 Litres (L)
Standard Error 0.032
|
0.307 Litres (L)
Standard Error 0.032
|
|
FVC Peak(0-3h) Change From Baseline
Week 48 (N=124, 130, 130)
|
0.361 Litres (L)
Standard Error 0.033
|
0.430 Litres (L)
Standard Error 0.032
|
0.413 Litres (L)
Standard Error 0.032
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in Trough (pre-dose) FVC measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Trough FVC Change From Baseline
Week 24 (N=126, 131, 134)
|
0.154 Litres (L)
Standard Error 0.035
|
0.246 Litres (L)
Standard Error 0.034
|
0.206 Litres (L)
Standard Error 0.034
|
|
Trough FVC Change From Baseline
Week 48 (N=124, 130, 130)
|
0.280 Litres (L)
Standard Error 0.035
|
0.341 Litres (L)
Standard Error 0.034
|
0.333 Litres (L)
Standard Error 0.034
|
SECONDARY outcome
Timeframe: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeksPopulation: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Outcome measures
| Measure |
Placebo Respimat
n=126 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=131 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=134 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FVC AUC (0-3h) Change From Baseline
|
0.130 Litres (L)
Standard Error 0.030
|
0.235 Litres (L)
Standard Error 0.029
|
0.207 Litres (L)
Standard Error 0.029
|
SECONDARY outcome
Timeframe: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at Week 24Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
FVC change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FVC Change From Baseline at Each Individual Timepoint
10 minutes pre-dose (Week 24) (N=124, 131, 134)
|
0.154 Litres (L)
Standard Error 0.035
|
0.246 Litres (L)
Standard Error 0.034
|
0.206 Litres (L)
Standard Error 0.034
|
|
FVC Change From Baseline at Each Individual Timepoint
30 minutes post-dose (Week 24) (N=124, 131, 134)
|
0.144 Litres (L)
Standard Error 0.032
|
0.222 Litres (L)
Standard Error 0.031
|
0.211 Litres (L)
Standard Error 0.031
|
|
FVC Change From Baseline at Each Individual Timepoint
1 hour post-dose (Week 24) (N=124, 131, 134)
|
0.142 Litres (L)
Standard Error 0.032
|
0.252 Litres (L)
Standard Error 0.031
|
0.202 Litres (L)
Standard Error 0.031
|
|
FVC Change From Baseline at Each Individual Timepoint
2 hours post-dose (Week 24) (N=124, 131, 134)
|
0.117 Litres (L)
Standard Error 0.033
|
0.230 Litres (L)
Standard Error 0.031
|
0.210 Litres (L)
Standard Error 0.032
|
|
FVC Change From Baseline at Each Individual Timepoint
3 hours post-dose (Week 24) (N=124, 131, 134)
|
0.118 Litres (L)
Standard Error 0.033
|
0.233 Litres (L)
Standard Error 0.032
|
0.210 Litres (L)
Standard Error 0.032
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at weeks 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Use of PRN (Pro re Nata) Rescue Medication Per Day
Week 24 (N=122, 130, 133)
|
-0.437 Number of puffs of rescue medication
Standard Error 0.079
|
-0.603 Number of puffs of rescue medication
Standard Error 0.077
|
0.646 Number of puffs of rescue medication
Standard Error 0.077
|
|
Use of PRN (Pro re Nata) Rescue Medication Per Day
Week 48 (N=120, 123, 127)
|
-0.484 Number of puffs of rescue medication
Standard Error 0.079
|
0.638 Number of puffs of rescue medication
Standard Error 0.078
|
0.685 Number of puffs of rescue medication
Standard Error 0.078
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during daytime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Use of PRN Rescue Medication During Daytime
Week 24 (N=121, 130, 133)
|
-0.234 Number of puffs of rescue medication
Standard Error 0.055
|
-0.350 Number of puffs of rescue medication
Standard Error 0.053
|
-0.375 Number of puffs of rescue medication
Standard Error 0.053
|
|
Use of PRN Rescue Medication During Daytime
Week 48 (N=119, 123, 125)
|
-0.247 Number of puffs of rescue medication
Standard Error 0.055
|
-0.372 Number of puffs of rescue medication
Standard Error 0.053
|
-0.378 Number of puffs of rescue medication
Standard Error 0.053
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during nighttime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Use of PRN Rescue Medication During Nighttime
Week 24 (N=122, 130, 130)
|
-0.178 Number of puffs of rescue medication
Standard Error 0.051
|
-0.274 Number of puffs of rescue medication
Standard Error 0.050
|
-0.304 Number of puffs of rescue medication
Standard Error 0.050
|
|
Use of PRN Rescue Medication During Nighttime
Week 48 (N=119, 122, 125)
|
-0.198 Number of puffs of rescue medication
Standard Error 0.052
|
-0.298 Number of puffs of rescue medication
Standard Error 0.050
|
-0.301 Number of puffs of rescue medication
Standard Error 0.050
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Peak Expiratory Flow (PEF) a.m. Change From Baseline
Week 24 (N=122, 130, 130)
|
14.153 Litres per min (L/min)
Standard Error 4.556
|
22.660 Litres per min (L/min)
Standard Error 4.406
|
21.646 Litres per min (L/min)
Standard Error 4.434
|
|
Peak Expiratory Flow (PEF) a.m. Change From Baseline
Week 48 (N=119, 122, 125)
|
20.824 Litres per min (L/min)
Standard Error 4.581
|
26.362 Litres per min (L/min)
Standard Error 4.440
|
29.598 Litres per min (L/min)
Standard Error 4.466
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PEF p.m. Change From Baseline
Week 24 (N= 121, 130, 133)
|
3.179 Litres per min (L/min)
Standard Error 4.597
|
15.539 Litres per min (L/min)
Standard Error 4.444
|
17.325 Litres per min (L/min)
Standard Error 4.464
|
|
PEF p.m. Change From Baseline
Week 48 (N=119, 123, 125)
|
17.100 Litres per min (L/min)
Standard Error 4.622
|
15.219 Litres per min (L/min)
Standard Error 4.475
|
21.276 Litres per min (L/min)
Standard Error 4.504
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in the peak expiratory flow variability based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PEF Variability Change From Baseline
Week 24 (N=121, 129, 128)
|
-1.204 Percentage of PEF
Standard Error 0.826
|
-0.942 Percentage of PEF
Standard Error 0.798
|
-1.038 Percentage of PEF
Standard Error 0.803
|
|
PEF Variability Change From Baseline
Week 48 (N=117, 120, 121)
|
-0.320 Percentage of PEF
Standard Error 0.835
|
-0.048 Percentage of PEF
Standard Error 0.814
|
-0.899 Percentage of PEF
Standard Error 0.818
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 a.m Change From Baseline
Week 24 (N=122, 130, 130)
|
0.191 Litres
Standard Error 0.041
|
0.209 Litres
Standard Error 0.039
|
0.126 Litres
Standard Error 0.039
|
|
FEV1 a.m Change From Baseline
Week 48 (N=119, 122, 125)
|
0.236 Litres
Standard Error 0.041
|
0.259 Litres
Standard Error 0.040
|
0.221 Litres
Standard Error 0.040
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
FEV1 p.m. Change From Baseline
Week 24 (N=121, 129, 128)
|
0.167 Litres (L)
Standard Error 0.042
|
0.142 Litres (L)
Standard Error 0.041
|
0.092 Litres (L)
Standard Error 0.041
|
|
FEV1 p.m. Change From Baseline
Week 48 (N=119, 123, 125)
|
0.202 Litres (L)
Standard Error 0.042
|
0.208 Litres (L)
Standard Error 0.041
|
0.159 Litres (L)
Standard Error 0.041
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Interviewer Administered Asthma Control Questionnaire (ACQ-IA) total score after 24 and 48 weeks of treatment. The ACQ-IA is a scale containing 7 questions. Each question has a 7 point scale which ranges from 0 to 6. A score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ-IA total score is calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
ACQ-IA Total Score
Week 24 (N=126, 131, 134)
|
1.017 Units on a Scale
Standard Error 0.062
|
0.897 Units on a Scale
Standard Error 0.060
|
0.835 Units on a Scale
Standard Error 0.060
|
|
ACQ-IA Total Score
Week 48 (N=124, 130, 130)
|
0.817 Units on a Scale
Standard Error 0.062
|
0.752 Units on a Scale
Standard Error 0.060
|
0.723 Units on a Scale
Standard Error 0.061
|
SECONDARY outcome
Timeframe: Weeks 24 and 48Population: FAS, missing data for patients not withdrawn from the study were either categorised as no change or based on available data, withdrawn patients were imputed based upon discontinuation reason
Responder categories based on the ACQ-IA total score after 24 and 48 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 \<change from trial baseline \<0.5) and worsening (change from trial baseline ≥0.5). No statistical testing was performed for ACQ-IA total score responders. The ACQ-IA is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
ACQ-IA Responder Analysis
Responders at Week 24
|
97 Patients
|
108 Patients
|
118 Patients
|
|
ACQ-IA Responder Analysis
No Change at Week 24
|
34 Patients
|
27 Patients
|
16 Patients
|
|
ACQ-IA Responder Analysis
Worsening at Week 24
|
0 Patients
|
0 Patients
|
1 Patients
|
|
ACQ-IA Responder Analysis
Responder at Week 48
|
114 Patients
|
118 Patients
|
117 Patients
|
|
ACQ-IA Responder Analysis
No Change at Week 48
|
16 Patients
|
14 Patients
|
17 Patients
|
|
ACQ-IA Responder Analysis
Worsening at Week 48
|
1 Patients
|
3 Patients
|
1 Patients
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Standardised Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) total score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). Total Score is calculated as mean of all 23 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PAQLQ(S) Total Score
Week 24 (N= 126, 131, 134)
|
5.966 Units on a Scale
Standard Error 0.065
|
6.142 Units on a Scale
Standard Error 0.063
|
6.093 Units on a Scale
Standard Error 0.062
|
|
PAQLQ(S) Total Score
Week 48 (N=124, 130, 130)
|
6.309 Units on a Scale
Standard Error 0.065
|
6.288 Units on a Scale
Standard Error 0.063
|
6.327 Units on a Scale
Standard Error 0.063
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
PAQLQ(S) symptom domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score was calculated as the mean of the items in the domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PAQLQ(S) Symptom Domain Score
Week 24 (N=126, 131, 134)
|
5.840 Units on a Scale
Standard Error 0.076
|
6.015 Units on a Scale
Standard Error 0.074
|
5.967 Units on a Scale
Standard Error 0.073
|
|
PAQLQ(S) Symptom Domain Score
Week 48 (N=124, 130, 130)
|
6.195 Units on a Scale
Standard Error 0.076
|
6.177 Units on a Scale
Standard Error 0.074
|
6.199 Units on a Scale
Standard Error 0.074
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
PAQLQ(S) activity limitation domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PAQLQ(S) Activity Limitation Domain Score
Week 24 (N= 126, 131, 134)
|
5.898 Units on a Scale
Standard Error 0.069
|
6.089 Units on a Scale
Standard Error 0.067
|
6.023 Units on a Scale
Standard Error 0.067
|
|
PAQLQ(S) Activity Limitation Domain Score
Week 48 (N=124, 130, 130)
|
6.249 Units on a Scale
Standard Error 0.070
|
6.284 Units on a Scale
Standard Error 0.068
|
6.319 Units on a Scale
Standard Error 0.067
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
PAQLQ(S) emotional function domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
PAQLQ(S) Emotional Function Domain Score
Week 24 (N=126, 131, 134)
|
6.157 Units on a Scale
Standard Error 0.067
|
6.323 Units on a Scale
Standard Error 0.065
|
6.298 Units on a Scale
Standard Error 0.064
|
|
PAQLQ(S) Emotional Function Domain Score
Week 48 (N=124, 130, 130)
|
6.481 Units on a Scale
Standard Error 0.067
|
6.420 Units on a Scale
Standard Error 0.065
|
6.491 Units on a Scale
Standard Error 0.065
|
SECONDARY outcome
Timeframe: Weeks 24 and 48.Population: FAS, missing data for patients not withdrawn from the study were either categorised as no change or based on available data, withdrawn patients were imputed based upon discontinuation reason.
Responders in PAQLQ(S) at weeks 24 and 48. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≥0.5), no change (-0.5 \<change from trial baseline \<0.5) and worsening (change from trial baseline ≤-0.5). No statistical testing was performed for PAQLQ(S) total score responders. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control).
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Responders in PAQLQ(S) at Weeks 24 and 48
Responders at Week 24
|
67 Patients
|
82 Patients
|
73 Patients
|
|
Responders in PAQLQ(S) at Weeks 24 and 48
No Change at Week 24
|
58 Patients
|
47 Patients
|
56 Patients
|
|
Responders in PAQLQ(S) at Weeks 24 and 48
Worsening at Week 24
|
6 Patients
|
6 Patients
|
6 Patients
|
|
Responders in PAQLQ(S) at Weeks 24 and 48
Responders at Week 48
|
89 Patients
|
96 Patients
|
92 Patients
|
|
Responders in PAQLQ(S) at Weeks 24 and 48
No Change at Week 48
|
39 Patients
|
33 Patients
|
42 Patients
|
|
Responders in PAQLQ(S) at Weeks 24 and 48
Worsening at Week 48
|
3 Patients
|
6 Patients
|
1 Patients
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in nighttime awakenings based on the weekly mean at weeks 24 and 48. Nighttime awakenings was assessed by the question "Did you wake up during the night due to your asthma?" from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Nighttime Awakenings
Week 24 (N=122, 130, 130)
|
-0.070 Units on a scale
Standard Error 0.030
|
-0.079 Units on a scale
Standard Error 0.029
|
-0.144 Units on a scale
Standard Error 0.029
|
|
Change From Baseline in Nighttime Awakenings
Week 48 (N=119, 122, 125)
|
-0.101 Units on a scale
Standard Error 0.030
|
-0.131 Units on a scale
Standard Error 0.029
|
-0.127 Units on a scale
Standard Error 0.029
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in morning asthma symptoms based on the weekly mean at weeks 24 and 48. Morning asthma symptoms was assessed by the question "how were your asthma symptoms this morning?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Morning Asthma Symptoms
Week 24 (N=122, 130, 130)
|
-0.138 Units on a scale
Standard Error 0.039
|
-0.138 Units on a scale
Standard Error 0.038
|
-0.220 Units on a scale
Standard Error 0.038
|
|
Change From Baseline in Morning Asthma Symptoms
Week 48 (N=119, 122, 125)
|
-0.177 Units on a scale
Standard Error 0.039
|
-0.230 Units on a scale
Standard Error 0.038
|
-0.221 Units on a scale
Standard Error 0.038
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in daytime asthma symptoms based on the weekly mean at weeks 24 and 48. Daytime asthma symptoms was assessed by the question "how were your asthma symptoms during the day?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Daytime Asthma Symptoms
Week 24 (N=121, 130, 133)
|
-0.204 Units on a scale
Standard Error 0.041
|
-0.243 Units on a scale
Standard Error 0.040
|
-0.263 Units on a scale
Standard Error 0.040
|
|
Change From Baseline in Daytime Asthma Symptoms
Week 48 (N=119, 123, 125)
|
-0.261 Units on a scale
Standard Error 0.042
|
-0.272 Units on a scale
Standard Error 0.041
|
-0.312 Units on a scale
Standard Error 0.041
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in daytime activity limitations based on the weekly mean at weeks 24 and 48. Daytime activity limitations was assessed by the question "how limited were you in your activities today because of your asthma?" from the e-diary. Scores range from 1 (not limited) to 5 (totally limited). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Daytime Activity Limitations
Week 24 (N=121, 130, 133)
|
-0.181 Units on a scale
Standard Error 0.039
|
-0.212 Units on a scale
Standard Error 0.038
|
-0.240 Units on a scale
Standard Error 0.038
|
|
Change From Baseline in Daytime Activity Limitations
Week 48 (N=119, 123, 125)
|
-0.227 Units on a scale
Standard Error 0.039
|
-0.238 Units on a scale
Standard Error 0.038
|
-0.259 Units on a scale
Standard Error 0.038
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in daytime experiences of shortness of breath based on the weekly mean at weeks 24 and 48. Daytime experiences of shortness of breath was assessed by the question "how much shortness of breath did you experience during the day" from the e-diary. Scores range from 1 (none) to 5 (a very great deal). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Daytime Experiences of Shortness of Breath
Week 24 (N=121, 130, 133)
|
-0.134 Units on a scale
Standard Error 0.039
|
-0.178 Units on a scale
Standard Error 0.038
|
-0.240 Units on a scale
Standard Error 0.038
|
|
Change From Baseline in Daytime Experiences of Shortness of Breath
Week 48 (N=119, 123, 125)
|
-0.219 Units on a scale
Standard Error 0.039
|
-0.231 Units on a scale
Standard Error 0.038
|
-0.253 Units on a scale
Standard Error 0.038
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at weeks 24 and 48. Daytime experiences of wheeze or cough was assessed by the question "did you experience wheeze or cough during the day?" from the e-diary. Scores range from 1 (not at all) to 5 (all the time). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Daytime Experiences of Wheeze or Cough
Week 24 (N=121, 130, 133)
|
-0.261 Units on a scale
Standard Error 0.046
|
-0.307 Units on a scale
Standard Error 0.045
|
-0.355 Units on a scale
Standard Error 0.045
|
|
Change From Baseline in Daytime Experiences of Wheeze or Cough
Week 48 (N=119, 123, 125)
|
-0.340 Units on a scale
Standard Error 0.047
|
-0.337 Units on a scale
Standard Error 0.045
|
-0.393 Units on a scale
Standard Error 0.046
|
SECONDARY outcome
Timeframe: Baseline and Week 24, Baseline and Week 48.Population: FAS, missing data at a visit was imputed by the available data from the patient at that visit. Completely missing data were handled by the statistical model.
Change from baseline in asthma symptom-free days based on the weekly mean at weeks 24 and 48. A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary (electronic diary) and no use of rescue medication reported via the eDiary during that day. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.
Outcome measures
| Measure |
Placebo Respimat
n=131 Participants
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 Participants
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 Participants
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Change From Baseline in Asthma Symptom-free Days
Week 24 (N=122, 130, 133)
|
0.135 Days
Standard Error 0.036
|
0.176 Days
Standard Error 0.034
|
0.172 Days
Standard Error 0.035
|
|
Change From Baseline in Asthma Symptom-free Days
Week 48 (N=120, 123, 127)
|
0.151 Days
Standard Error 0.036
|
0.170 Days
Standard Error 0.035
|
0.180 Days
Standard Error 0.035
|
Adverse Events
Placebo
Tio R2.5
Tio R5
Serious adverse events
| Measure |
Placebo
n=131 participants at risk
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 participants at risk
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 participants at risk
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.74%
1/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Immune system disorders
Anaphylactic reaction
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.74%
1/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.74%
1/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Gastroenteritis
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Renal abscess
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Injury, poisoning and procedural complications
Concussion
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Injury, poisoning and procedural complications
Fall
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Injury, poisoning and procedural complications
Skull fracture
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.5%
2/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
1.5%
2/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus haematoma
|
0.76%
1/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
0.00%
0/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
Other adverse events
| Measure |
Placebo
n=131 participants at risk
Inhalation of placebo solution (2 puffs) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R2.5
n=135 participants at risk
Inhalation of 2.5mcg tiotropium (Tio R2.5) solution (2 puffs of 1.25mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
Tio R5
n=135 participants at risk
Inhalation of 5mcg tiotropium (Tio R5) solution (2 puffs of 2.5mcg) once daily for 48 weeks delivered by the Respimat inhaler, as add on therapy on top of usual care.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
9.9%
13/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
11.1%
15/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
8.9%
12/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Rhinitis
|
5.3%
7/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
3.7%
5/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
1.5%
2/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Investigations
Peak expiratory flow rate decreased
|
20.6%
27/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
23.0%
31/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
21.5%
29/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
43.5%
57/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
36.3%
49/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
34.1%
46/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
6.1%
8/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
3.0%
4/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
4.4%
6/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Respiratory tract infection
|
12.2%
16/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
8.1%
11/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
9.6%
13/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
|
Infections and infestations
Respiratory tract infection viral
|
6.1%
8/131 • From first drug intake until 30 days after last drug intake, up to day 407.
|
5.9%
8/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
5.9%
8/135 • From first drug intake until 30 days after last drug intake, up to day 407.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER