Trial Outcomes & Findings for Dynamic Hyperinflation and Tiotropium (NCT NCT00569270)

NCT ID: NCT00569270

Last Updated: 2019-08-20

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: 30 days
• Results posted on: 2019-08-20

Participant Flow

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

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.

Participant milestones

Measure	Tiotropium 18 µg Capsule First, Then Placebo tiotropium 18 µg capsule for 1 month versus placebo. To study bronchodilation and effect following metronome paced hyperventilation and induced dynamic hyperinflation of active tiotropium versus placebo	Placebo First, Then Tiotropium Bromide 18 µg tiotropium 18 µg capsule for 1 month versus placebo. To study bronchodilation and effect following metronome paced hyperventilation and induced dynamic hyperinflation of active tiotropium versus placebo
Period: First Intervention STARTED	15	15
Period: First Intervention COMPLETED	15	14
Period: First Intervention NOT COMPLETED	0	1
Period: Second Intervention STARTED	15	14
Period: Second Intervention 29 Days	15	14
Period: Second Intervention COMPLETED	15	14
Period: Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Tiotropium 18 µg Capsule First, Then Placebo tiotropium 18 µg capsule for 1 month versus placebo. To study bronchodilation and effect following metronome paced hyperventilation and induced dynamic hyperinflation of active tiotropium versus placebo	Placebo First, Then Tiotropium Bromide 18 µg tiotropium 18 µg capsule for 1 month versus placebo. To study bronchodilation and effect following metronome paced hyperventilation and induced dynamic hyperinflation of active tiotropium versus placebo
Period: First Intervention Protocol Violation	0	1

Baseline Characteristics

Dynamic Hyperinflation and Tiotropium

Baseline characteristics by cohort

Measure	Entire Study Population n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants
Average participant age +/- SD	70 years STANDARD_DEVIATION 9 • n=5 Participants
FVC (forced vital capacity) FVC (L)	2.9 liters STANDARD_DEVIATION 1.2 • n=5 Participants
FVC (forced vital capacity) FVC (L) post 180 µg albuterol sulfate MDI	3.3 liters STANDARD_DEVIATION 1.2 • n=5 Participants
FVC FVC percent of liters predicted	86 percentage of liters expected STANDARD_DEVIATION 17 • n=5 Participants
FVC FVC post 180 µg albuterol percent of ltrs predict	95 percentage of liters expected STANDARD_DEVIATION 16 • n=5 Participants
FEV1(L) (forces expiratory volume) observed FEV1(L)	1.6 liters STANDARD_DEVIATION 0.6 • n=5 Participants
FEV1(L) (forces expiratory volume) observed FEV1(L) post 180 ug albuterol sulfate MDI	1.8 liters STANDARD_DEVIATION 0.6 • n=5 Participants
FEV1 (L) percent predicted FEV1 percent liters predicted	61 percentage of liters expected STANDARD_DEVIATION 69 • n=5 Participants
FEV1 (L) percent predicted FEV1 percent liters predicted post albuterol	8 percentage of liters expected STANDARD_DEVIATION 6 • n=5 Participants
FEV1/FVC percentage	56 percentage of liters expected STANDARD_DEVIATION 8 • n=5 Participants
SGaw (Lps/cmH2O/L) (specific airway conductance)	0.10 Lps/cmH2O/L STANDARD_DEVIATION 0.08 • n=5 Participants
FRC (L) (functional residual capacity) observed	3.9 liters STANDARD_DEVIATION 0.8 • n=5 Participants
FRC percent of liters predicted	138 percentage of liters predicted STANDARD_DEVIATION 29 • n=5 Participants
RV (L) (residual volume) observed	2.9 liters STANDARD_DEVIATION 0.1 • n=5 Participants
RV (L) - % predicted	131 percentage STANDARD_DEVIATION 37 • n=5 Participants
TLC (L) (total lung capacity) observed	5.9 liters STANDARD_DEVIATION 1.3 • n=5 Participants
TLC Percent of liters predicted	109 percentage of liters predicted STANDARD_DEVIATION 16 • n=5 Participants
D(L)CO(SB) - ml/min/mmHg observed (Single-breath diffusing capacity )	14 ml/min/mmHg STANDARD_DEVIATION 5 • n=5 Participants
D(L)CO(SB) - ml/min/mmHg % predicted	69 ml/min/mmHg STANDARD_DEVIATION 23 • n=5 Participants

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response:Peak FEV1(L)(Forced Expiratory Volume in One Second)-	1.74 liters Standard Deviation 0.58	1.82 liters Standard Deviation 0.59

PRIMARY outcome

Timeframe: 30 days

Population: Includes groups randomized to receive placebo first and Tiotropium first.

Lung function studies (mean +/- SD): peak FRC after 30 days (+2h) of placebo or tiotropium in 29 moderate COPD patients.

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response:Peak FRC (L) (Functional Residual Capacity)	3.80 Liters Standard Deviation 0.79	3.72 Liters Standard Deviation 0.84

PRIMARY outcome

Timeframe: 30 days

Population: Peak FVC after 30 days (+2h) of tiotropium versus placebo in 29 moderate COPD patients.

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Peak FVC (L) (Forced Vital Capacity)- Tiotropium and Placebo	3.17 liters Standard Deviation 1.13	3.27 liters Standard Deviation 1.16

PRIMARY outcome

Timeframe: 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.

Lung function studies (mean +/- SD) - Peak inspiratory capacity after 30 days (+2h)of tiotropium versus placebo in 29 moderate COPD patients. Inspiratory capacity- liters

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Peak IC (L) - (Inspiratory Capacity) - Tiotropium Versus Placebo	2.12 liters Standard Deviation 0.82	2.24 liters Standard Deviation 0.80

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
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 0.10	0.66 percentage of FRC/TLC Standard Deviation 0.17

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Peak TLC (L) (Total Lung Capacity)- Tiotropium or Placebo	5.91 liters Standard Deviation 1.22	5.82 liters Standard Deviation 1.35

PRIMARY outcome

Timeframe: 30 days

Population: Lung function studies Trough FEV1(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

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)

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough FEV1 (L)- (Forced Expiratory Volume) Tiotropium Versus Placebo	1.68 liters Standard Deviation 0.54	1.71 liters Standard Deviation 0.56

PRIMARY outcome

Timeframe: 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)

Lung function studies Trough FRC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients. Functional residual capacity(liters)

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough FRC (L)- Tiotropium Versus Placebo	3.84 liters Standard Deviation 0.84	3.66 liters Standard Deviation 0.88

PRIMARY outcome

Timeframe: 30 days

Population: Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

Lung function studies Trough FVC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough FVC (L)- (Forced Vital Capacity) Tiotropium Versus Placebo	3.12 liters Standard Deviation 1.10	3.15 liters Standard Deviation 1.13

PRIMARY outcome

Timeframe: 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

Lung function studies (Trough IC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients Trough inspiratory capacity- liters

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough IC (L) Inspiratory Capacity - Tiotropium Versus Placebo	2.17 liters Standard Deviation 0.77	2.11 liters Standard Deviation 0.83

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough FRC/TLC (Functional Residual Capacity/Total Lung Capacity)- Tiotropium Versus Placebo	0.64 percentage of FRC/TLC Standard Deviation 0.09	0.62 percentage of FRC/TLC Standard Deviation 0.09

PRIMARY outcome

Timeframe: 30 days

Population: Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

Lung function studies Trough TLC(mean +/- SD) after 30 days(-1h) of tiotropium versus placebo in 29 moderate COPD patients

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
Bronchodilator Response: Trough TLC (L) (Total Lung Capacity)- Tiotropium Versus Placebo	5.99 liters Standard Deviation 1.18	5.86 liters Standard Deviation 1.25

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
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	1.76 liters Standard Deviation 0.70
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	1.80 liters Standard Deviation 0.70
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 0.80	1.80 liters Standard Deviation 0.74

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Placebo n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium n=29 Participants Includes groups randomized to receive placebo first and Tiotropium first.
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	5.84 liters Standard Deviation 1.35
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	5.78 liters Standard Deviation 1.14

SECONDARY outcome

Timeframe: baseline to 30 days

Population: High-resolution, thin-section scans of the lung were obtained from a subset of 19 patients.

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

Outcome measures

Measure	Placebo n=19 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium Includes groups randomized to receive placebo first and Tiotropium first.
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	—

SECONDARY outcome

Timeframe: baseline to 30 days

Population: Analysis was carried out per protocol

Correlation between change in inspiratory capacity (L) post metronome paced hyperventilation induced dynamic hyperinflation and extent of lung ct scored emphysema

Outcome measures

Measure	Placebo n=19 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium Includes groups randomized to receive placebo first and Tiotropium first.
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	—

SECONDARY outcome

Timeframe: baseline to trough tiotropium

Population: High resolution, thin-section scans of the lung were obtained in a subset of 19 patients.

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

Outcome measures

Measure	Placebo n=19 Participants Includes groups randomized to receive placebo first and Tiotropium first.	Tiotropium Includes groups randomized to receive placebo first and Tiotropium first.
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	—

Adverse Events

Tiotropium Bromide 18 µg, Capsule,

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Arthur F Gelb MD Principal Investigator

Arthur F Gelb MD

Phone: 562-633-2204

Email: afgelb@msn.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place