Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 1

Change from baseline in trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study medication. Trough FEV1 is defined as FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after the last inhalation of drug.

Time frame: Baseline and 12 weeks

Population: Treated Set (TS) including patients who had trough FEV1 data at both baseline and week 12

Percentage 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, was defined as a primary endpoint but was not analysed numerically, so this endpoint is presented instead. 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 randomised and took at least one dose of study drug, 157 patients (79 Tiotropium and 78 placebo) were included in this set.

Change from baseline of Trough FEV1 (forced expiratory volume in one 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. This endpoint was analysed using combined data, as specified in the analysis plan.

Time frame: Baseline and 12 weeks

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.

Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug. This endpoint was analysed using combined data, as specified in the analysis plan.

Time frame: Baseline and 12 weeks

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.

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) including patients who had trough FVC data at both baseline and week 12

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. 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. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.

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. This endpoint was analysed using combined data, as specified in the analysis plan.

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.

Percentage 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. This endpoint was analysed using combined data, as specified in the analysis plan.

Time frame: from date of hospital discharge prior to randomization up to readmission days >1 and <31 days

Population: Treated set of the pooled twin studies 205.478 and 205.477

Percentage of patients with adverse clinical event during on study, which is defined as the combined endpoint of chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalisation, 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

Percentage 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. 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

Percentage 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 a newly prescribed maintenance respiratory medication (i.e. bronchodilators including theophyllines and PDE4-inhibitors). 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

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: This endpoint was not analysed due to the trials being terminated prematurely due to low patient enrollment and the limited amount of data.