Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00975195
First received: September 10, 2009
Last updated: February 9, 2015
Last verified: February 2015
Results First Received: December 23, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Pulmonary Disease, Chronic Obstructive
Interventions: Drug: tiotropium inhalation
Drug: salmeterol xinafoate
Drug: fluticasone propionate
Drug: placebo matched for fluticasone propionate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Fluticasone Maintenance 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d., 50 μg salmeterol b.i.d.,and 500 μg fluticasone b.i.d. for 52 weeks (randomised treatment period).
Fluticasone Withdrawal 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d.and 50 μg salmeterol b.i.d. for 52 weeks, in combination with a stepwise withdrawal of fluticasone, consisting of 250μg fluticasone b.i.d for 6 weeks, followed by 100μg fluticasone b.i.d for 6 weeks, followed by placebo for 40 weeks (randomised treatment period).

Participant Flow:   Overall Study
    Fluticasone Maintenance     Fluticasone Withdrawal  
STARTED     1244     1244  
COMPLETED     1016 [1]   1011 [1]
NOT COMPLETED     228     233  
Adverse Event                 108                 101  
Lack of Efficacy                 6                 6  
Protocol Violation                 27                 23  
Lost to Follow-up                 9                 7  
Withdrawal by Subject                 48                 61  
Other reason not defined above                 29                 33  
Not treated                 1                 2  
[1] Includes open-label treatment if appropriate



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated Set (TS) which included all patients who were dispensed study medication and were documented to have taken ≥1 dose of randomised treatment.

Reporting Groups
  Description
Fluticasone Maintenance 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d., 50 μg salmeterol b.i.d.,and 500 μg fluticasone b.i.d. for 52 weeks (randomised treatment period).
Fluticasone Withdrawal 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d.and 50 μg salmeterol b.i.d. for 52 weeks, in combination with a stepwise withdrawal of fluticasone, consisting of 250μg fluticasone b.i.d for 6 weeks, followed by 100μg fluticasone b.i.d for 6 weeks, followed by placebo for 40 weeks (randomised treatment period).
Total Total of all reporting groups

Baseline Measures
    Fluticasone Maintenance     Fluticasone Withdrawal     Total  
Number of Participants  
[units: participants]
  1243     1242     2485  
Age  
[units: years]
Mean (Standard Deviation)
  63.6  (8.6)     64.0  (8.4)     63.8  (8.5)  
Gender  
[units: participants]
     
Female     230     206     436  
Male     1013     1036     2049  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to First Moderate or Severe On-treatment COPD Exacerbation   [ Time Frame: During randomised treatment, up to 488 days ]

2.  Secondary:   Number of Moderate or Severe On-treatment COPD Exacerbations   [ Time Frame: During randomised treatment, up to 488 days ]

3.  Secondary:   Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation   [ Time Frame: During randomised treatment, up to 488 days ]

4.  Secondary:   Time to First Severe On-treatment COPD Exacerbation   [ Time Frame: During randomised treatment, up to 488 days ]

5.  Secondary:   Number of Severe On-treatment COPD Exacerbations   [ Time Frame: During randomised treatment, up to 488 days ]

6.  Secondary:   Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation.   [ Time Frame: During randomised treatment, up to 488 days ]

7.  Secondary:   Time to First On-treatment COPD Exacerbation   [ Time Frame: During randomised treatment, up to 488 days ]

8.  Secondary:   Number of On-treatment COPD Exacerbations   [ Time Frame: During randomised treatment, up to 488 days ]

9.  Secondary:   Proportion of Patients With at Least One On-treatment COPD Exacerbation   [ Time Frame: During randomised treatment, up to 488 days ]

10.  Secondary:   Severity of On-treatment COPD Exacerbations   [ Time Frame: During randomised treatment, up to 488 days ]

11.  Secondary:   Change in On-treatment Lung Function as Measured by Trough FEV1   [ Time Frame: Baseline and week 6, 12, 18 and 52 visits ]

12.  Secondary:   Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale   [ Time Frame: Baseline and week 18 and 52 visits ]

13.  Secondary:   Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI)   [ Time Frame: Baseline and week 18 and 52 visits ]

14.  Secondary:   Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT)   [ Time Frame: Baseline and week 18 and 52 visits ]

15.  Secondary:   Change in On-treatment BODE Index   [ Time Frame: Baseline and week 18 and 52 visits ]

16.  Secondary:   Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain   [ Time Frame: Baseline and week 12, 18 and 52 visits ]

17.  Secondary:   Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain   [ Time Frame: Baseline and week 12, 18 and 52 visits ]

18.  Secondary:   Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain   [ Time Frame: Baseline and week 12, 18 and 52 visits ]

19.  Secondary:   Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain   [ Time Frame: Baseline and week 12, 18 and 52 visits ]

20.  Secondary:   Change in On-treatment FEV1 as Measured by Home Based Spirometry   [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ]

21.  Secondary:   Change in On-treatment FVC as Measured by Home Based Spirometry   [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ]

22.  Secondary:   Change in On-treatment PEFR as Measured by Home Based Spirometry   [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ]

23.  Secondary:   Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain   [ Time Frame: Baseline and week 27 and 52 visits ]

24.  Secondary:   Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain   [ Time Frame: Baseline and week 27 and 52 visits ]

25.  Secondary:   Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain   [ Time Frame: Baseline and week 27 and 52 visits ]

26.  Secondary:   Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score   [ Time Frame: Baseline and week 27 and 52 visits ]

27.  Secondary:   Change in On-treatment Physician Global Evaluation   [ Time Frame: Baseline and week 27 and 52 visits ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Additional secondary endpoints were listed in the original protocol. Those endpoints are of exploratory nature only and were not considered relevant for trial conclusions. For more information see tab “Full Text Review”, section “More Information".


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim

Publications automatically indexed to this study:

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00975195     History of Changes
Other Study ID Numbers: 352.2046, 2007-002522-29
Study First Received: September 10, 2009
Results First Received: December 23, 2014
Last Updated: February 9, 2015
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
China: Food and Drug Administration
Denmark: The Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Greece: Ethics Committee
Hungary: National Institute of Pharmacy, H-1051 Budapest
Italy: Ethics Committee
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Multicentre Ethics Committee/Medsafe
Philippines: Bureau of Food and Drugs
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Tunisia: Office of Pharmacies and Medicines
Turkey: Ministry of Health Central Ethics Committee
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)