COPD
Conditions
Brief summary
We will detect dynamic hyperinflation (DH) in 40 COPD (chronic obstructive pulmonary disease) patients with moderately severe disease using metronome paced hyperventilation (MPH) with inspiratory capacity as the primary end point. Hypothesis: Is tiotropium capable of lung volume protecting inspiratory capacity from MPH induced DH vs placebo in a randomized crossover double blinded study.
Detailed description
Study completed with 29 patients studied. Data is being analyzed to evaluate trough and peak effect of 18 µg tiotropium vs placebo on FEV 1 (L)(forced expiratory capacity in one second), inspiratory capacity and functional residual volume. In addition, we will study the effect of 18 µg tiotropium vs placebo on metronome paced hyperventilation induced dynamic hyperinflation. We will also evaluate the effect of tiotropium induced increase in IC (inspiratory capacity) vs extent of emphysema as evaluated on high resolution thin section CT lung
Interventions
DRUGPlacebo
Procedure/Surgery - tiotropium 18ug capsule daily for 1 month vs placebo to study the effect of trough and peak effect on bronchodilation and effect of metronome paced hyperventilation induced dynamic hyperinflation
Sponsors
Boehringer Ingelheim
Pfizer
Gelb, Arthur F., M.D.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Moderately severe COPD patients age 40-85 yr with post 180ug albuterol FEV 1 between 60 and 79% predicted and FEV 1/FVC \< 70%. * Smoking history \> 10 pack yr. * Clinically stable X 6 weeks. * No oxygen usage.
Exclusion criteria
* History of asthma * Clinically unstable * Any other significant medical problem precluding full cooperation for study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo | one hour before intervention & 2 hrs. after after 30 days | Total lung capacity before and after metronome paced hyperventilation induced dynamic hyperinflation in tiotropium cohort versus placebo. Difference between TLC measured at one hour before intervention & 2 hrs. after after 30 days of treatment with either placebo or tiotropium |
| Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo | 30 days | Lung function studies Trough FRC/TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough Functional residual capacity/total lung capacity - percentage |
| Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo | 30 days | Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients |
| IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | baseline and 30 days (+2h) post dose | IC measurement before and after metronome paced hyperventilation-induced dynamic hyperinflation at baseline and in tiotropium and placebo groups. Measure ratio of functional residual capacity divided by total lung capacity at baseline and after 30 days of tiotropium versus placebo |
| Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)- | 30 days | Lung function studies (mean +/- SD): peak FEV1 (+2h) after 30 days of placebo or tiotropium in 29 moderate COPD patients. FEV1 = Forced expiratory volume in one second |
| Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity) | 30 days | Lung function studies (mean +/- SD): peak FRC after 30 days (+2h) of placebo or tiotropium in 29 moderate COPD patients. |
| Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo | 30 days | Lung function studies (mean +/- SD) of peak forced vital capaciy (L) after 30 days (+2h) of tiotropium versus placebo in 29 moderate COPD patients. Forced vital capacity - liters |
| Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo | 30 days | Lung function studies (mean +/- SD) - Peak inspiratory capacity after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Inspiratory capacity- liters |
| Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo | 30 days | Lung function studies (mean +/- SD) peak Peak FRC/TLC after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity/total lung capacity - percentage |
| Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo | 30 days | Net change in lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients. Total lung capacity - liters |
| Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo | 30 days | Lung function studies Trough FEV1(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Forced expiratory volume in 1s (liters) |
| Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo | 30 days | Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters) |
| Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo | 30 days | Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients |
| Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo | 30 days | Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IC (Inspiratory Capacity, L) Post Mph (Metronome Paced Hyperventilation) Induced dh (Dynamic Hyperinflation) After Tiotropium and Extent of Lung CT Scored Emphysema | baseline to 30 days | Correlation between change in inspiratory capacity (L) post metronome paced hyperventilation induced dynamic hyperinflation and extent of lung ct scored emphysema |
| Extent of Lung CT Scored Emphysema and and Lung Function of FRC/TLC (Functional Residual Capacity(L)/Total Lung Capacity (L) After Tiotropium | baseline to trough tiotropium | Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema |
| Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium | baseline to 30 days | Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to FEV 1; correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema; measures include increase in FEV1 from baseline to peak tiotropium |
Countries
Canada, United States
Participant flow
Recruitment details
Patients with COPD (chronic obstructive pulmonary disease), GOLD (Global Initiative for Chronic Obstructive Lung Disease)Stage 2 were recruited from pulmonary out-patient offices at Mt. Sinai Hosp. Toronto and from Arthur F Gelb MD Lakewood, Calif from June 2009 thru January 2010
Pre-assignment details
We recruited 30 patients with smoking history \>20 pack yr with documented GOLD Stage 2 moderate COPD who were clinically stable for at least 6 weeks prior to the present study and were not on oxygen or oral corticosteroids.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive placebo first and Tiotropium first. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period: First Intervention | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Average participant age +/- SD | 70 years STANDARD_DEVIATION 9 |
| D(L)CO(SB) - ml/min/mmHg observed (Single-breath diffusing capacity ) | 14 ml/min/mmHg STANDARD_DEVIATION 5 |
| D(L)CO(SB) - ml/min/mmHg % predicted | 69 ml/min/mmHg STANDARD_DEVIATION 23 |
| FEV1/FVC percentage | 56 percentage of liters expected STANDARD_DEVIATION 8 |
| FEV1(L) (forces expiratory volume) observed FEV1(L) | 1.6 liters STANDARD_DEVIATION 0.6 |
| FEV1(L) (forces expiratory volume) observed FEV1(L) post 180 ug albuterol sulfate MDI | 1.8 liters STANDARD_DEVIATION 0.6 |
| FEV1 (L) percent predicted FEV1 percent liters predicted | 61 percentage of liters expected STANDARD_DEVIATION 69 |
| FEV1 (L) percent predicted FEV1 percent liters predicted post albuterol | 8 percentage of liters expected STANDARD_DEVIATION 6 |
| FRC (L) (functional residual capacity) observed | 3.9 liters STANDARD_DEVIATION 0.8 |
| FRC percent of liters predicted | 138 percentage of liters predicted STANDARD_DEVIATION 29 |
| FVC FVC percent of liters predicted | 86 percentage of liters expected STANDARD_DEVIATION 17 |
| FVC FVC post 180 µg albuterol percent of ltrs predict | 95 percentage of liters expected STANDARD_DEVIATION 16 |
| FVC (forced vital capacity) FVC (L) | 2.9 liters STANDARD_DEVIATION 1.2 |
| FVC (forced vital capacity) FVC (L) post 180 µg albuterol sulfate MDI | 3.3 liters STANDARD_DEVIATION 1.2 |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment United States | 23 participants |
| RV (L) - % predicted | 131 percentage STANDARD_DEVIATION 37 |
| RV (L) (residual volume) observed | 2.9 liters STANDARD_DEVIATION 0.1 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
| SGaw (Lps/cmH2O/L) (specific airway conductance) | 0.10 Lps/cmH2O/L STANDARD_DEVIATION 0.08 |
| TLC (L) (total lung capacity) observed | 5.9 liters STANDARD_DEVIATION 1.3 |
| TLC Percent of liters predicted | 109 percentage of liters predicted STANDARD_DEVIATION 16 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)-
Lung function studies (mean +/- SD): peak FEV1 (+2h) after 30 days of placebo or tiotropium in 29 moderate COPD patients. FEV1 = Forced expiratory volume in one second
Time frame: 30 days
Population: Lung function studies (mean +/- SD): peak FEV1 (+2h) after 30 days of placebo or tiotropium in 29 moderate COPD patients. FEV1 = Forced expiratory volume in one second
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)- | 1.74 liters | Standard Deviation 0.58 |
| Tiotropium | Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)- | 1.82 liters | Standard Deviation 0.59 |
Comparison: Mean difference of Peak FEV1 of tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.027Mixed Models Analysis
Primary
Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity)
Lung function studies (mean +/- SD): peak FRC after 30 days (+2h) of placebo or tiotropium in 29 moderate COPD patients.
Time frame: 30 days
Population: Includes groups randomized to receive placebo first and Tiotropium first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity) | 3.80 Liters | Standard Deviation 0.79 |
| Tiotropium | Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity) | 3.72 Liters | Standard Deviation 0.84 |
Comparison: Mean difference of Peak FRC in tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.318Mixed Models Analysis
Primary
Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo
Lung function studies (mean +/- SD) peak Peak FRC/TLC after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity/total lung capacity - percentage
Time frame: 30 days
Population: Lung function studies (mean +/- SD) peak Peak FRC/TLC after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity/total lung capacity - percentage
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo | 0.65 percentage of FRC/TLC | Standard Deviation 0.1 |
| Tiotropium | Bronchodilator Response: Peak FRC/TLC Percentage (Functional Residual Capacity(L)/Total Lung Capacity(L) - Tiotropium or Placebo | 0.66 percentage of FRC/TLC | Standard Deviation 0.17 |
Comparison: Mean difference of Peak FRC/TLC of tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.615Regression, Logistic
Primary
Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo
Lung function studies (mean +/- SD) of peak forced vital capaciy (L) after 30 days (+2h) of tiotropium versus placebo in 29 moderate COPD patients. Forced vital capacity - liters
Time frame: 30 days
Population: Peak FVC after 30 days (+2h) of tiotropium versus placebo in 29 moderate COPD patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo | 3.17 liters | Standard Deviation 1.13 |
| Tiotropium | Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo | 3.27 liters | Standard Deviation 1.16 |
Comparison: Mean difference of Peak FVC of tiotropium minus placebo.29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.078Mixed Models Analysis
Primary
Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo
Lung function studies (mean +/- SD) - Peak inspiratory capacity after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Inspiratory capacity- liters
Time frame: 30 days
Population: Net change in lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo | 2.12 liters | Standard Deviation 0.82 |
| Tiotropium | Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo | 2.24 liters | Standard Deviation 0.8 |
Comparison: Mean difference of Peak IC of tiotropium minus placebo.29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.067Mixed Models Analysis
Primary
Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo
Net change in lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients. Total lung capacity - liters
Time frame: 30 days
Population: Net change in lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo | 5.91 liters | Standard Deviation 1.22 |
| Tiotropium | Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo | 5.82 liters | Standard Deviation 1.35 |
Comparison: 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.325Mixed Models Analysis
Primary
Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo
Lung function studies Trough FEV1(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Forced expiratory volume in 1s (liters)
Time frame: 30 days
Population: Lung function studies Trough FEV1(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo | 1.68 liters | Standard Deviation 0.54 |
| Tiotropium | Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo | 1.71 liters | Standard Deviation 0.56 |
Comparison: 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.345Mixed Models Analysis
Primary
Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo
Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters)
Time frame: 30 days
Population: Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo | 3.84 liters | Standard Deviation 0.84 |
| Tiotropium | Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo | 3.66 liters | Standard Deviation 0.88 |
Comparison: Mean difference of Trough FRC(L) in tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.068Mixed Models Analysis
Primary
Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo
Lung function studies Trough FRC/TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough Functional residual capacity/total lung capacity - percentage
Time frame: 30 days
Population: Lung function studies Trough FRC/TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough Functional residual capacity/total lung capacity - percentage
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo | 0.64 percentage of FRC/TLC | Standard Deviation 0.09 |
| Tiotropium | Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo | 0.62 percentage of FRC/TLC | Standard Deviation 0.09 |
Comparison: Mean difference of Trough FRC/TLC of tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: -0.02Mixed Models Analysis
Primary
Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo
Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
Time frame: 30 days
Population: Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo | 3.12 liters | Standard Deviation 1.1 |
| Tiotropium | Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo | 3.15 liters | Standard Deviation 1.13 |
Comparison: Mean difference of trough FVC in tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.589Mixed Models Analysis
Primary
Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo
Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters
Time frame: 30 days
Population: Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo | 2.17 liters | Standard Deviation 0.77 |
| Tiotropium | Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo | 2.11 liters | Standard Deviation 0.83 |
Comparison: Mean difference of Trough IC of tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.922Mixed Models Analysis
Primary
Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo
Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
Time frame: 30 days
Population: Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo | 5.99 liters | Standard Deviation 1.18 |
| Tiotropium | Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo | 5.86 liters | Standard Deviation 1.25 |
Comparison: Mean difference of Trough TLC (L) of tiotropium minus placebo. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: -0.13Mixed Models Analysis
Primary
IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline
IC measurement before and after metronome paced hyperventilation-induced dynamic hyperinflation at baseline and in tiotropium and placebo groups. Measure ratio of functional residual capacity divided by total lung capacity at baseline and after 30 days of tiotropium versus placebo
Time frame: baseline and 30 days (+2h) post dose
Population: Inspiratory capacity (IC) (mean +/- SD) from baseline and after 30 days of tiotropium versus placebo in 29 moderate COPD patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Baseline IC (inspiratory capacity) | 2.09 liters | Standard Deviation 0.83 |
| Placebo | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Placebo IC | 2.17 liters | Standard Deviation 0.82 |
| Placebo | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Tiotropium IC | 2.24 liters | Standard Deviation 0.8 |
| Tiotropium | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Baseline IC (inspiratory capacity) | 1.76 liters | Standard Deviation 0.7 |
| Tiotropium | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Placebo IC | 1.80 liters | Standard Deviation 0.7 |
| Tiotropium | IC (Inspiratory Capacity L)and Metronome Paced Hyperventilation-induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo and Baseline | Tiotropium IC | 1.80 liters | Standard Deviation 0.74 |
Comparison: Change in IC before and after dynamic hyperinflation. 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: 0.0001Mixed Models Analysis
Primary
TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo
Total lung capacity before and after metronome paced hyperventilation induced dynamic hyperinflation in tiotropium cohort versus placebo. Difference between TLC measured at one hour before intervention & 2 hrs. after after 30 days of treatment with either placebo or tiotropium
Time frame: one hour before intervention & 2 hrs. after after 30 days
Population: lung function studies (mean +/- SE) from baseline to trough (-1h) and peak (+2h) after 30 days of tiotropium versus placebo in 29 moderate COPD patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo | Before DH (dynamic hyperinflation) | 5.96 liters | Standard Deviation 1.22 |
| Placebo | TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo | After DH | 5.84 liters | Standard Deviation 1.13 |
| Tiotropium | TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo | Before DH (dynamic hyperinflation) | 5.84 liters | Standard Deviation 1.35 |
| Tiotropium | TLC (L) Before and After Metronome Paced Hyperventilation Induced Dynamic Hyperinflation in Tiotropium Cohort Versus Placebo | After DH | 5.78 liters | Standard Deviation 1.14 |
Comparison: 29 patients needed to achieve a power of 80% at a significant alpha level of 5% using projected sample inspiratory capacity of 2.23+/- 0.5L post tiotropium compared to baseline inspiratory capacity 2.0+/-0.5Lp-value: >0.05Mixed Models Analysis
Secondary
Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium
Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to FEV 1; correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema; measures include increase in FEV1 from baseline to peak tiotropium
Time frame: baseline to 30 days
Population: High-resolution, thin-section scans of the lung were obtained from a subset of 19 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extent of Lung CT Scored Emphysema and and Lung Function of FEV1(l) After Tiotropium | 13.68 percentage of lung tissue | Standard Deviation 18.84 |
Comparison: Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema; measure includes change in FEV1 post tiotropiump-value: 0.96Spearman rho
Secondary
Extent of Lung CT Scored Emphysema and and Lung Function of FRC/TLC (Functional Residual Capacity(L)/Total Lung Capacity (L) After Tiotropium
Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema
Time frame: baseline to trough tiotropium
Population: High resolution, thin-section scans of the lung were obtained in a subset of 19 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Extent of Lung CT Scored Emphysema and and Lung Function of FRC/TLC (Functional Residual Capacity(L)/Total Lung Capacity (L) After Tiotropium | 13.68 percentage of lung tissue | Standard Deviation 18.84 |
Comparison: Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysemap-value: 0.36Spearman rho
Secondary
IC (Inspiratory Capacity, L) Post Mph (Metronome Paced Hyperventilation) Induced dh (Dynamic Hyperinflation) After Tiotropium and Extent of Lung CT Scored Emphysema
Correlation between change in inspiratory capacity (L) post metronome paced hyperventilation induced dynamic hyperinflation and extent of lung ct scored emphysema
Time frame: baseline to 30 days
Population: Analysis was carried out per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IC (Inspiratory Capacity, L) Post Mph (Metronome Paced Hyperventilation) Induced dh (Dynamic Hyperinflation) After Tiotropium and Extent of Lung CT Scored Emphysema | 13.68 percentage of lung tissue | Standard Deviation 18.84 |
Comparison: Correlation between improved lung function after tiotropium and extent of lung CT scored emphysema with respect to ratio functional residual capacity divided by total lung capacity. Specifically, correlation of tiotropium induced bronchodilation and extent of lung ct scored emphysema (19 patients); measures include change in IC at trough tiotropium.p-value: 0.4Spearman rho