Trial Outcomes & Findings for Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation (NCT NCT00578968)

NCT ID: NCT00578968

Last Updated: 2012-06-26

Results Overview

Cardiac index: A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m\^2) to yield the cardiac index.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 36 participants
• Primary outcome timeframe: First visit of first study period
• Results posted on: 2012-06-26

Participant Flow

Participants were recruited at the Mayo Clinic, Rochester, Minnesota from October 2006 to August 2008. The first period compared cardiovascular response in COPD patients to healthy controls prior to the intervention. In the second period the COPD patients were randomized to drug or placebo; the controls did not take part in this period.

Participant milestones

Measure	Tiotropium Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.	Healthy Controls Healthy age and gender matched controls were recruited for comparing cardiovascular responses to participants with chronic obstructive pulmonary disease prior to the intervention.
Baseline (Prior to Intervention) STARTED	12	12	12
Baseline (Prior to Intervention) COMPLETED	12	12	12
Baseline (Prior to Intervention) NOT COMPLETED	0	0	0
Intervention STARTED	12	12	0
Intervention COMPLETED	12	12	0
Intervention NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation

Baseline characteristics by cohort

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.	Healthy Controls n=12 Participants Healthy age and gender matched controls were recruited for comparing cardiovascular responses to participants with chronic obstructive pulmonary disease prior to the intervention.	Total n=36 Participants Total of all reporting groups
Age Continuous	61.2 years STANDARD_DEVIATION 5.7 • n=5 Participants	56.3 years STANDARD_DEVIATION 9.4 • n=7 Participants	58.4 years STANDARD_DEVIATION 10.6 • n=5 Participants	58.6 years STANDARD_DEVIATION 9.0 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	36 participants n=4 Participants
Height	169.1 cm STANDARD_DEVIATION 10.3 • n=5 Participants	172.5 cm STANDARD_DEVIATION 8.0 • n=7 Participants	173.0 cm STANDARD_DEVIATION 7.7 • n=5 Participants	171.3 cm STANDARD_DEVIATION 8.7 • n=4 Participants
Weight	91.9 kg STANDARD_DEVIATION 30.2 • n=5 Participants	89.6 kg STANDARD_DEVIATION 17.9 • n=7 Participants	80.4 kg STANDARD_DEVIATION 11.3 • n=5 Participants	86.7 kg STANDARD_DEVIATION 21.2 • n=4 Participants
Body Mass Index (BMI)	32.1 kg/m^2 STANDARD_DEVIATION 10.4 • n=5 Participants	29.9 kg/m^2 STANDARD_DEVIATION 4.4 • n=7 Participants	26.8 kg/m^2 STANDARD_DEVIATION 3.1 • n=5 Participants	29.4 kg/m^2 STANDARD_DEVIATION 7.0 • n=4 Participants
Body Surface Area (BSA)	2.06 m^2 STANDARD_DEVIATION 0.35 • n=5 Participants	2.07 m^2 STANDARD_DEVIATION 0.25 • n=7 Participants	1.96 m^2 STANDARD_DEVIATION 0.17 • n=5 Participants	2.02 m^2 STANDARD_DEVIATION 0.26 • n=4 Participants

PRIMARY outcome

Timeframe: First visit of first study period

Cardiac index: A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting Cardiac Index (CI)	2.4 L/min/m^2 Standard Deviation 0.71	2.36 L/min/m^2 Standard Deviation 0.51

PRIMARY outcome

Timeframe: first visit of first study period

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the body surface area (BSA) (m^2).

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting Stroke Volume Index (SVI)	31.3 mL/m^2 Standard Deviation 11.5	39.7 mL/m^2 Standard Deviation 8.3

PRIMARY outcome

Timeframe: first visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Cardiac index (CI): A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Peak Exercise CI	5.34 L/min/m^2 Standard Deviation 1.39	6.70 L/min/m^2 Standard Deviation 1.66

PRIMARY outcome

Timeframe: first visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the BSA (m^2).

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Peak Exercise SVI	44.62 mL/m^2 Standard Deviation 9.0	50.06 mL/m^2 Standard Deviation 12.49

SECONDARY outcome

Timeframe: First visit of first study period

Population: All COPD participants were included, prior to randomization in the second period of the study.

Vital capacity is the maximum amount of air a person can expel from the lungs after a maximum inspiration. A person's vital capacity can be measured by a spirometer which can be a wet or regular spirometer. In combination with other physiological measurements, the vital capacity can help make a diagnosis of underlying lung disease.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting Forced Vital Capacity (FVC)	3.29 Liters Standard Deviation 1.02	4.20 Liters Standard Deviation 0.98

SECONDARY outcome

Timeframe: First visit of first study period

Predicted normal values for vital capacity can be calculated online (based on previous research) and depends on age, sex, height, weight and ethnicity. Percentage was calculated by observed FVC/predicted FVC X 100.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting FVC as Percentage of Predicted Forced Vital Capacity (FVC)	78.3 percentage of predicted FVC Standard Deviation 13.8	99.4 percentage of predicted FVC Standard Deviation 14.8

SECONDARY outcome

Timeframe: first visit of first study period

FEV_1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting Forced Expiratory Volume in 1 Second (FEV_1)	1.74 L/sec Standard Deviation 0.70	3.22 L/sec Standard Deviation 0.74

SECONDARY outcome

Timeframe: first visit of first study period

Predicted normal values for Forced Expiratory Volume in 1 second can be calculated online (based on previous research) and depends on age, sex, height, weight and ethnicity. Percentage was calculated by observed FEV_1/predicted FEV_1 X 100.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Resting FEV_1 as Percentage of Predicted FEV_1	51.6 percentage of predicted FEV_1 Standard Deviation 14.1	97.5 percentage of predicted FEV_1 Standard Deviation 12.4

SECONDARY outcome

Timeframe: first visit of first study period, second visit of first study period

Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Heart rate was measured in the first study period prior to the intervention at resting and at peak exercise states.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Heart Rate (HR) for All COPD Participants Versus Healthy Control Groups Baseline Resting, V1-1st study period	79.4 beats per minute (bpm) Standard Deviation 13.7	72.7 beats per minute (bpm) Standard Deviation 10.4
Baseline Heart Rate (HR) for All COPD Participants Versus Healthy Control Groups Baseline Peak Exercise, V2-1st study period	127.8 beats per minute (bpm) Standard Deviation 23.4	153.6 beats per minute (bpm) Standard Deviation 16.8

SECONDARY outcome

Timeframe: second visit of first study period

VO_2 is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Peak Exercise Maximal Oxygen Consumption (VO_2)	1.52 L/min Standard Deviation 0.41	2.29 L/min Standard Deviation 0.60

SECONDARY outcome

Timeframe: second visit of first study period

Cardiac index: A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index.

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Peak Exercise Cardiac Index (CI)	6.02 L/min/m^2 Standard Deviation 1.65	7.61 L/min/m^2 Standard Deviation 2.14

SECONDARY outcome

Timeframe: second visit of first study period

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the BSA (m^2).

Outcome measures

Measure	Tiotropium n=24 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Baseline Peak Exercise Stroke Volume Index (SVI)	47.3 mL/m^2 Standard Deviation 11.0	52.7 mL/m^2 Standard Deviation 9.4

SECONDARY outcome

Timeframe: First study visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Vital capacity is the maximum amount of air a person can expel from the lungs after a maximum inspiration. A person's vital capacity can be measured by a spirometer which can be a wet or regular spirometer. In combination with other physiological measurements, the vital capacity can help make a diagnosis of underlying lung disease.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Resting Forced Vital Capacity (FVC)	2.79 Liters Standard Deviation 0.64	3.80 Liters Standard Deviation 1.10

SECONDARY outcome

Timeframe: First visit of first period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Predicted normal values for vital capacity can be calculated online (based on previous research) and depends on age, sex, height, weight and ethnicity. Percentage was calculated by observed FVC/predicted FVC X 100.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Resting FVC as Percentage of Predicted FVC	71.24 percentage of predicted FVC Standard Deviation 9.08	85.27 percentage of predicted FVC Standard Deviation 14.34

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal Control population did not take part in this measurement.

Vital capacity is the maximum amount of air a person can expel from the lungs after a maximum inspiration. A person's vital capacity can be measured by a spirometer which can be a wet or regular spirometer. In combination with other physiological measurements, the vital capacity can help make a diagnosis of underlying lung disease. Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Resting FVC Between Pretreatment in First Study Period and Post-treatment in Second Study Period	11.55 percentage of change in FVC Standard Deviation 15.27	-6.20 percentage of change in FVC Standard Deviation 11.03

SECONDARY outcome

Timeframe: first study visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

FEV_1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Resting FEV_1	1.48 L/sec Standard Deviation 0.49	2.00 L/sec Standard Deviation 0.80

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal controls did not take part in this measurement.

FEV_1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity. Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Resting FEV_1 Between Pretreatment in First Study Period and Post-treatment in Second Study Period	8.81 Percentage of change in FEV_1 Standard Deviation 11.86	-6.30 Percentage of change in FEV_1 Standard Deviation 1.98

SECONDARY outcome

Timeframe: first study visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Cardiac index (CI): A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Resting CI	2.31 L/min/m^2 Standard Deviation 0.72	2.49 L/min/m^2 Standard Deviation 0.73

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal controls did not take part in this measurement.

Cardiac index (CI): A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index. Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Resting CI Between Pretreatment in First Study Period and Post-treatment in Second Study Period	-4.91 percentage of change in CI Standard Deviation 26.80	-9.08 percentage of change in CI Standard Deviation 25.04

SECONDARY outcome

Timeframe: first study visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the BSA (m^2).

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Resting SVI	30.08 mL/m^2 Standard Deviation 12.59	32.55 mL/m^2 Standard Deviation 10.69

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal controls did not take part in this measurement.

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the BSA (m^2). Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Resting SVI Between Pretreatment in First Study Period and Post-treatment in Second Study Period	-3.80 Percentage of change in SVI Standard Deviation 34.54	-6.26 Percentage of change in SVI Standard Deviation 29.15

SECONDARY outcome

Timeframe: first study visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Heart rate was measured in the first study period prior to the intervention at resting and at peak exercise states.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Heart Rate (HR) in Tiotropium and Placebo Groups Pretreatment Resting HR, V1-1st study period	80.50 bpm Standard Deviation 15.37	78.33 bpm Standard Deviation 12.32
Pretreatment Heart Rate (HR) in Tiotropium and Placebo Groups Pretreatment Peak Exercise HR, V1-1st study period	120.17 bpm Standard Deviation 21.44	135.33 bpm Standard Deviation 23.67

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal control population did not take part in this measurement.

Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Resting HR Between Pretreatment in First Study Period and Post-treatment in Second Study Period	-7.05 Percentage of change in HR Standard Deviation 5.14	-1.32 Percentage of change in HR Standard Deviation 8.35

SECONDARY outcome

Timeframe: first visit of first study period

Population: Normal Control population did not take part in this measurement. Researchers collected this data V1 study period 1, but randomized subjects after V4 study period 1.

VO_2 is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise.

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Pretreatment Peak Exercise Maximal Oxygen Consumption (VO_2)	1.33 L/min Standard Deviation 0.33	1.65 L/min Standard Deviation 0.46

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal Control population did not take part in this measurement.

VO_2 is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise. Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Peak Exercise VO_2 Between Pretreatment in First Study Period and Post-treatment in Second Study Period	2.06 percentage of change in VO_2 Standard Deviation 12.76	-4.60 percentage of change in VO_2 Standard Deviation 10.27

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal control population did not take part in this measurement.

Cardiac index (CI): A cardiodynamic measure based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index. Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Peak Exercise CI Between Pretreatment in First Study Period and Post-treatment in Second Study Period	2.46 percentage of change in CI Standard Deviation 14.02	-11.80 percentage of change in CI Standard Deviation 21.29

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal control population did not take part in this measurement.

Stroke volume - the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the BSA (m^2). Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Peak Exercise SVI Between Pretreatment in First Study Period and Post-treatment in Second Study Period	3.11 percentage of change in SVI Standard Deviation 16.37	-4.95 percentage of change in SVI Standard Deviation 21.33

SECONDARY outcome

Timeframe: first visit of first study period, first visit of second study period (approximately 6 weeks later)

Population: Normal control population did not take part in this measurement.

Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute (bpm). Percentage change = final value - initial value/initial value x 100

Outcome measures

Measure	Tiotropium n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.	Placebo n=12 Participants Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose.
Percent Change in Peak Exercise HR Between Pretreatment in First Study Period and Post-treatment in Second Study Period	0.27 percentage of change in HR Standard Deviation 12.30	-7.05 percentage of change in HR Standard Deviation 5.14

Adverse Events

Tiotropium

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

Healthy Controls

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

Bruce D. Johnson, PhD

Mayo Clinic

Phone: 507-284-4441

Email: johnson.bruce@mayo.edu

Results disclosure agreements

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