Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation

This study has been completed.
Sponsor:
Collaborators:
Boehringer Ingelheim
Pfizer
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00578968
First received: December 20, 2007
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

This study is being done to examine the influence of Tiotropium (good or bad) on heart function at rest and during exercise in patients with moderate to severe chronic obstructive pulmonary disease (COPD).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
COPD
Drug: Tiotropium
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cardiac Limitations in Chronic Obstructive Pulmonary Disease: Benefits of Bronchodilation

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Baseline Resting Cardiac Index (CI) [ Time Frame: First visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Resting Stroke Volume Index (SVI) [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    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).

  • Pretreatment Peak Exercise CI [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Pretreatment Peak Exercise SVI [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Baseline Resting Forced Vital Capacity (FVC) [ Time Frame: First visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Resting FVC as Percentage of Predicted Forced Vital Capacity (FVC) [ Time Frame: First visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Resting Forced Expiratory Volume in 1 Second (FEV_1) [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    FEV_1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity.

  • Baseline Resting FEV_1 as Percentage of Predicted FEV_1 [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Heart Rate (HR) for All COPD Participants Versus Healthy Control Groups [ Time Frame: first visit of first study period, second visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Peak Exercise Maximal Oxygen Consumption (VO_2) [ Time Frame: second visit of first study period ] [ Designated as safety issue: No ]
    VO_2 is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise.

  • Baseline Peak Exercise Cardiac Index (CI) [ Time Frame: second visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Baseline Peak Exercise Stroke Volume Index (SVI) [ Time Frame: second visit of first study period ] [ Designated as safety issue: No ]
    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).

  • Pretreatment Resting Forced Vital Capacity (FVC) [ Time Frame: First study visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Pretreatment Resting FVC as Percentage of Predicted FVC [ Time Frame: First visit of first period ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Resting FVC Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Pretreatment Resting FEV_1 [ Time Frame: first study visit of first study period ] [ Designated as safety issue: No ]
    FEV_1 is the volume exhaled during the first second of a forced expiratory maneuver started from the level of total lung capacity.

  • Percent Change in Resting FEV_1 Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Pretreatment Resting CI [ Time Frame: first study visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Resting CI Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Pretreatment Resting SVI [ Time Frame: first study visit of first study period ] [ Designated as safety issue: No ]
    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).

  • Percent Change in Resting SVI Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Pretreatment Heart Rate (HR) in Tiotropium and Placebo Groups [ Time Frame: first study visit of first study period ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Resting HR Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Pretreatment Peak Exercise Maximal Oxygen Consumption (VO_2) [ Time Frame: first visit of first study period ] [ Designated as safety issue: No ]
    VO_2 is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise.

  • Percent Change in Peak Exercise VO_2 Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Percent Change in Peak Exercise CI Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Percent Change in Peak Exercise SVI Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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

  • Percent Change in Peak Exercise HR Between Pretreatment in First Study Period and Post-treatment in Second Study Period [ Time Frame: first visit of first study period, first visit of second study period (approximately 6 weeks later) ] [ Designated as safety issue: No ]
    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


Enrollment: 36
Study Start Date: October 2006
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tiotropium
Participants with chronic obstructive pulmonary disease randomized to this arm received a once daily oral inhalation of 18 mcg tiotropium powder.
Drug: Tiotropium
Participants received once daily Spiriva capsules for oral inhalation: 18 mcg tiotropium powder, for use with HandiHaler device.
Other Name: Spiriva
Placebo Comparator: 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.
Drug: Placebo
Participants randomized to this arm received a once daily oral inhalation of placebo powder to match the standard active comparator dose, using the HandiHaler device.
No Intervention: 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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Chronic obstructive pulmonary disease (COPD) participants-

Inclusion criteria:

  • Body Mass Index (BMI) <36
  • Moderate to severe COPD patient, (similar to or slightly better than Gold Guidelines Stage 2-3, forced expiratory volume in one second [FEV_1] <60% of age predicted)
  • Smoking history of 10 pack years or more
  • Clinical diagnosis of COPD
  • Not on daytime oxygen

Exclusion criteria:

  • Clinical diagnosis of asthma
  • Myocardial infarction within the last 6 months, or known ischemia
  • Serious uncontrolled cardiac arrhythmia (i.e., atrial fibrillation or ventricular tachycardia) or hospitalization for heart failure within the previous year
  • Known moderate to severe renal impairment
  • Known moderate to severe symptomatic prostatic hypertrophy or bladder neck obstruction
  • Known narrow angle glaucoma
  • Current radiation or chemotherapy for a malignant condition
  • Inability to give informed consent
  • On systemic corticosteroids at unstable doses or on regular daily doses of 20 mg or more of prednisone (or equivalent)
  • Not fully recovered from an exacerbation of COPD for at least 30 days
  • Inability to perform light to moderate activity for orthopedic reasons or who significantly desaturated with exercise (percentage of available hemoglobin that is saturated with oxygen [SaO_2] < 85% on screening test

Healthy controls -

Inclusion:

- Age and gender matched to COPD participants

Exclusion:

- Subjects who are unable to engage in exercise testing due to existing comorbidities

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578968

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Boehringer Ingelheim
Pfizer
Investigators
Principal Investigator: Bruce D Johnson, Ph.D Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Bruce Johnson, PhD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00578968     History of Changes
Other Study ID Numbers: 06-003434
Study First Received: December 20, 2007
Results First Received: May 22, 2012
Last Updated: May 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
COPD
Tiotropium
Spiriva

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tiotropium
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014