Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
A randomized, placebo-controlled, double-blind, parallel group, multi-center study to assess the safety and efficacy of tiotropium bromide (18 µg) delivered via the HandiHaler® in Chronic Obstructive Pulmonary Disease (COPD) subjects recovering from hospitalization for an acute exacerbation (Hospital Discharge Study 2)
Interventions
DRUGtiotropium bromide
18 mcg once a day (QD)
DRUGPlacebo
Once a day (QD)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The following inclusion criteria apply at Visit 0: 1. All subjects must sign an informed consent consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial and conducting any study procedures 2. Male or female subjects 40 years of age or older. 3. Hospitalization for a primary diagnosis of acute COPD exacerbation for =14 days. Determination of accuracy of admission diagnosis will be at the discretion of the investigator. 4. Patient reported hospital length of stay and discharge date (confirmed with hospital discharge summary/hospital records; however, medical record confirmation may occur following randomization). The following inclusion criteria apply at Visit 1: 5. Discharged from the hospital =10 days from date of randomization. 6. All subjects must have a diagnosis of COPD (P12-01205), and have documented airway obstruction with a post-bronchodilator Force Expiratory Volume in 1 second (FEV1)\\ Force vital capacity (FVC) \<0.7(See Section 5.1.2, Pulmonary Function Testing). The diagnosis of COPD can be made at Visit 1 if no Pulmonary Function Testing (PFT) data available within the past 12 months. 7. Subjects must be current or ex-smoker with a smoking history of =10 pack-years: Pack-years = Number of cigarettes/day x years of smoking 20 cigarettes/ pack 8. Subjects must be able to inhale medication in a competent manner from the HandiHaler® device (Appendix 10.1) and from a metered dose inhaler (MDI).
Exclusion criteria
The following exclusion criterion applies at Visit 0: 1. No more than 30 days of therapy with any long-acting inhaled anticholinergic over preceding 3 months prior to discharge from the hospital, and no therapy with any long acting anticholinergic post discharge (no use between hospital discharge and randomization) or any other restricted concomitant medications The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug. | Baseline and 12 weeks | Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug. Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug. |
| Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality. Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed. This endpoint was analysed using combined data, as specified in the analysis plan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | Baseline and week 12 | Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug. Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug. |
| Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | Baseline and week 12 | Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug. |
| Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study. A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following: 1\) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness. Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment. A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors). |
| Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study. All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures. Hospitalizations occurring on the same day as discharge were not considered a separate admission. |
| Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | from date of hospital discharge prior to randomization upto readmission days >1 and <31 days | Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed. Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1. The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days \>1 and \<31 days using the TS. |
| Change From Baseline of Trough FVC at 12 Weeks on Study Drug. | baseline and 12 weeks | Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug. |
| Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years | Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis. |
| Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS. |
| Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis. |
| Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | from first drug administration to the last timepoint with information of EXACT-PRO, Up to 2 years | Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported. Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average. Analysis based on Kaplan Meier estimate |
| Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years | Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS. |
| Percentage of Patients With Adverse Clinical Event During on Study. | from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years | Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality. |
Countries
United States
Participant flow
Pre-assignment details
Randomized, placebo-controlled, double blind, parallel group design involving an event-driven treatment period up to the close of the study and a minimum 30-day follow-up period up to the close of the study
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler. | 39 |
| Tiotropium Bromide (18 μg) Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler | 39 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Not Treated | 1 | 0 |
| Overall Study | Other than stated above | 3 | 0 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Tiotropium Bromide (18 μg) | Total |
|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 8.6 | 58.4 Years STANDARD_DEVIATION 7 | 59.2 Years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 39 | 23 / 39 |
| serious Total, serious adverse events | 9 / 39 | 10 / 39 |
Outcome results
Primary
Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug.
Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug. Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.
Time frame: Baseline and 12 weeks
Population: Treated Set (TS): The treated set included all patients randomized and who took at least one dose of the study drug. The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug. | 0.124 Litres | Standard Deviation 0.271 |
| Tiotropium Bromide (18 μg) | Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug. | 0.186 Litres | Standard Deviation 0.475 |
Primary
Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).
Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality. Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed. This endpoint was analysed using combined data, as specified in the analysis plan
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477 : This set includes all patients who were randomized and took at least one dose of the study drug, 157 patients (79 tiotropium and 78 placebo) were included in this set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | 47.4 Percentage of participants |
| Tiotropium Bromide (18 μg) | Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | 53.2 Percentage of participants |
Secondary
Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug. Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.
Time frame: Baseline and week 12
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.035 Litres | Standard Deviation 0.262 |
| Tiotropium Bromide (18 μg) | Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.185 Litres | Standard Deviation 0.384 |
Secondary
Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
Time frame: Baseline and week 12
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | -0.015 Litres | Standard Deviation 0.396 |
| Tiotropium Bromide (18 μg) | Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.278 Litres | Standard Deviation 0.447 |
Secondary
Change From Baseline of Trough FVC at 12 Weeks on Study Drug.
Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
Time frame: baseline and 12 weeks
Population: Treated Set (TS). The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Trough FVC at 12 Weeks on Study Drug. | 0.090 Litres | Standard Deviation 0.399 |
| Tiotropium Bromide (18 μg) | Change From Baseline of Trough FVC at 12 Weeks on Study Drug. | 0.282 Litres | Standard Deviation 0.558 |
Secondary
Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 58.0 patient years |
| Tiotropium Bromide (18 μg) | Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 60.2 patient years |
Secondary
Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.
Time frame: start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 58.0 Patient years |
| Tiotropium Bromide (18 μg) | Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 60.2 Patient years |
Secondary
Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.8 hospitalizations per patient year |
| Tiotropium Bromide (18 μg) | Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.6 hospitalizations per patient year |
Secondary
Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
Time frame: start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 1.3 exacerbations per patient year |
| Tiotropium Bromide (18 μg) | Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 0.9 exacerbations per patient year |
Secondary
Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed. Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1. The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days \>1 and \<31 days using the TS.
Time frame: from date of hospital discharge prior to randomization upto readmission days >1 and <31 days
Population: Treated Set of the pooled twin studies 205.478 and 205.477
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 5.1 percentage of participants |
| Tiotropium Bromide (18 μg) | Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 5.1 percentage of participants |
Secondary
Percentage of Patients With Adverse Clinical Event During on Study.
Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With Adverse Clinical Event During on Study. | 35.9 percentage of participants |
| Tiotropium Bromide (18 μg) | Percentage of Patients With Adverse Clinical Event During on Study. | 46.2 percentage of participants |
Secondary
Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).
Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study. All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures. Hospitalizations occurring on the same day as discharge were not considered a separate admission.
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | 26.9 percentage of participants |
| Tiotropium Bromide (18 μg) | Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987). | 26.6 percentage of participants |
Secondary
Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study. A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following: 1\) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness. Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment. A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors).
Time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
Population: Treated Set of the pooled twin studies 205.478 and 205.477
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 44.9 percentage of participants |
| Tiotropium Bromide (18 μg) | Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 40.5 percentage of participants |
Secondary
Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported. Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average. Analysis based on Kaplan Meier estimate
Time frame: from first drug administration to the last timepoint with information of EXACT-PRO, Up to 2 years
Population: Patients who had baseline and post-baseline measurements of EXACT-PRO.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 94.0 Percentage of patients recovered |
| Tiotropium Bromide (18 μg) | Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987) | 88.0 Percentage of patients recovered |