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Evaluation of the Long- Term Effects of Spiriva on Lung Function in COPD Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00144339
First received: September 2, 2005
Last updated: July 10, 2012
Last verified: July 2012
History of Changes
  Purpose

The primary objective of this trial is to determine whether daily treatment with tiotropium (Spiriva®, Bromuro de Tiotropio®) inhalation capsule via HandiHaler® reduces the rate of decline in lung function over time in patients with COPD.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
 Drug: tiotropium
Drug: placebo
 Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Trial Assessing the Rate of Decline of Lung Function With Tiotropium 18 Mcg Inhalation Capsule Once Daily in Patients With Chronic Obstructive Pulmonary Disease (COPD).

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1.

  • Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of forced expiratory volume in one second (FEV1) measured after bronchodilation. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1.


Secondary Outcome Measures:
  • Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. ]
    Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1

  • Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]
    Rate of decline of forced expiratory volume in one second (FEV1) measured after the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1

  • Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of forced vital capacity (FVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC

  • Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of forced vital capacity (FVC) measured after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC

  • Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of slow vital capacity (SVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC

  • Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years [ Time Frame: From day 30 to 4 years ]
    Rate of decline of slow vital capacity (SVC) measured after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC

  • Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score [ Time Frame: From month 6 to 4 years ]
    SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). A negative rate of decline shows decreasing SGRQ total score (or improved health) over time, while a positive value shows increasing score (or worsen health).

  • Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. ]
    Rate of decline of forced vital capacity (FVC) before bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC

  • Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]
    Rate of decline of forced vital capacity (FVC) after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC

  • Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]
    Rate of decline slow vital capacity (SVC) before bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC

  • Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment [ Time Frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days ]
    Rate of decline of slow vital capacity (SVC) after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC

  • Time to First Exacerbation [ Time Frame: From Day 1 to 4 years ]
    Chronic obstructive pulmonary disease (COPD) exacerbation

  • Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year [ Time Frame: Day 1 to 4 years ]
  • Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation [ Time Frame: Day 1 to 4 years ]
  • Number of Exacerbation Days Per Patient Year [ Time Frame: Day 1 to 4 years ]
    Number of exacerbation days normalized by treatment exposure

  • Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization [ Time Frame: Day 1 to 4 years ]
  • Number and Percentage of Patients With Time to First Exacerbation Leading to Hospitalization [ Time Frame: From Day 1 to 4 years ]
    Hazard ratio of time to first exacerbation leading to hospitalization

  • Number of Exacerbation Leading to Hospitalization [ Time Frame: From Day 1 to 4 years ]
    Estimated number of exacerbations leading to hospitalizations per patient year

  • Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization [ Time Frame: From Day 1 to 4 years ]
    Number of days with chronic obstructive pulmonary disease (COPD) exacerbation leading to hospitalization (normalized by treatment exposure)

  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 [ Time Frame: Month 1 ]
    Estimated FEV1 before bronchodilator at Month 1

  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 [ Time Frame: Month 1 ]
    Estimated forced expiratory volume in one second (FEV1) after bronchodilator at month 1

  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 [ Time Frame: Month 6 ]
    Estimated forced expiratory volume in one second (FEV1) before bronchodilator at month 6

  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 [ Time Frame: Month 6 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 [ Time Frame: Month 42 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 [ Time Frame: Month 42 ]
    Estimated FEV1 after bronchodilator at Month 42

  • Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 [ Time Frame: Month 48 ]
  • Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 [ Time Frame: Month 48 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1 [ Time Frame: Month 1 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1 [ Time Frame: Month 1 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6 [ Time Frame: Month 6 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6 [ Time Frame: Month 6 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42 [ Time Frame: Month 42 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42 [ Time Frame: Month 42 ]
  • Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48 [ Time Frame: Month 48 ]
  • Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48 [ Time Frame: Month 48 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1 [ Time Frame: Month 1 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1 [ Time Frame: Month 1 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6 [ Time Frame: Month 6 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6 [ Time Frame: Month 6 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12 [ Time Frame: Month 12 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18 [ Time Frame: Month 18 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24 [ Time Frame: Month 24 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30 [ Time Frame: Month 30 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36 [ Time Frame: Month 36 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42 [ Time Frame: Month 42 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42 [ Time Frame: Month 42 ]
  • Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48 [ Time Frame: Month 48 ]
  • Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48 [ Time Frame: Month 48 ]
  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6 [ Time Frame: Month 6 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12 [ Time Frame: Month 12 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18 [ Time Frame: Month 18 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24 [ Time Frame: Month 24 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30 [ Time Frame: Month 30 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36 [ Time Frame: Month 36 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42 [ Time Frame: Month 42 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48 [ Time Frame: Month 48 ]
    • SGRQ total score summarizes the impact of COPD on overall patient's health status.
    • Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
    • The scale is continuous.
    • Rate of decline shows the yearly change of SGRQ total score.

  • Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days ]
    On-treatment defined as day 1 to completion of double blinded treatment plus 30 days

  • Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) [ Time Frame: Day 1 to day 1470 ]
    All cause mortality vital status information was followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used.

  • Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) [ Time Frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days ]
    The primary cause of death was adjudicated by an external committee prior to unblinding; on-treatment defined as day 1 to completion of double blinded treatment plus 30 days

  • Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) [ Time Frame: Day 1 to day 1470 ]
    The primary cause of death was adjudicated by an external committee prior to unblinding; vital status was information followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used


Enrollment: 5993
Study Start Date: December 2002
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent.
  • Male or female patients 40 years of age or older.
  • Smoking history of at least 10 pack years.
  • Diagnosis of COPD with post bronchodilator FEV1 less than or equal to 70% of predicted normal and FEV1<70% of FVC and on stable respiratory medication.

Exclusion Criteria:

  • Significant diseases other than COPD which in the opinion of the investigator may put the patient at risk or influence the patients ability to participate.
  • Myocardial infarction in past 6 months.
  • Unstable or life threatening arrhythmia in past year.
  • Hospitalization for NYHA heart failure class III or IV in past year.
  • Active tuberculosis.
  • Asthma.
  • Pulmonary resection.
  • Malignancy treated with radiation or chemotherapy in past 5 years.
  • Respiratory infection in 4 weeks prior to screening.
  • Known hypersensitivity to anticholinergic drugs or components.
  • Known moderate to severe renal impairment.
  • Known narrow angle glaucoma.
  • Significant symptomatic BPH or bladder neck obstruction.
  • Need for oxygen therapy >12 hr/day.
  • Use of oral corticosteroids at unstable doses or >10 mg/day.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00144339

  Show 490 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

Additional Information:
Related Info  This link exits the ClinicalTrials.gov site
Related Info  This link exits the ClinicalTrials.gov site

No publications provided by Boehringer Ingelheim Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00144339     History of Changes
Other Study ID Numbers: 205.235
Study First Received: September 2, 2005
Results First Received: February 21, 2009
Last Updated: July 10, 2012
Health Authority: Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Hungary: National Institute of Pharmacy, H-1051 Budapest
Lithuania: State Medicines Control Agency, LT-01132 Vilnius
Poland: Urzad Rejestracji Produktow Leczniczych, Wyrobow, Medycznych i Produktow Biobojczych
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
Slovenia: Agency for Medicinal Products, SI-1000 Ljubljana
Australia: Responsilble Ethics Committee
New Zealand: Multicentre Ethics Committee/Medsafe
Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna
Belgium: Federal Agency for Medicines and Health Products
United States: Food and Drug Administration
France: AFFSAPS
Hong Kong: Dept. of Health of Hong Kong
Italy: Comitato Etico Az. Osp. Univ. Pisana di Pisa
Malaysia: Ministry of Health, Malaysia
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Portugal: INFARMED - National Authority of Medicines and Health Products, IP
Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnología)
Taiwan: Department of Health, Executive Yuan, Taiwan
Philippines: Department of Health, Republic of the Philippines
Thailand: Ministry of Public Health
Finland: Finnish Medicines Agency
Singapore: Health Science Authority, Ministry of Health
Switzerland: Swissmedic
Turkey: Ministry of Health Central Ethics Committee
Great Britain: MHRA
South Africa: Medicines Control Council

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

ClinicalTrials.gov processed this record on May 19, 2013