Comparison of Tiotropium in the HandiHaler Versus the Respimat in Chronic Obstructive Pulmonary Disease

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT01126437

First received: May 6, 2010

Last updated: May 20, 2014

Last verified: May 2014

History of Changes

Results First Received: May 20, 2014

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double-Blind; Primary Purpose: Treatment
Condition:	Pulmonary Disease, Chronic Obstructive
Interventions:	Drug: tiotropium 18 mcg Drug: tiotropium 1.25 mcg (2 actuations/day) Drug: tiotropium 2.5 mcg (2 actuations/day)

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This table summarizes study treatment disposition and reasons for discontinuation of study medication. Deaths that caused discontinuation from trial medications are included in AEs. Lost to follow−up indicates status at time of discontinuation of trial medication. Vital status was ascertained for 99.7% of patients.

Reporting Groups

Description

Tiotropium 2.5 mcg and Placebo

Patients receive one of the active tiotropium arms daily

tiotropium 1.25 mcg (2 actuations/day): soft mist inhaler 2 actuations=2 puffs/day

Tiotropium 5 mcg and Placebo

Patients receive one of the active tiotropium arms daily

tiotropium 2.5 mcg (2 actuations/day): soft mist inhaler (2 actuations=2 puffs/day)

Tiotropium 18 mcg and Placebo

Patients receive one of the active tiotropium arms daily

tiotropium 18 mcg: HandiHaler

Participant Flow: Overall Study

	Tiotropium 2.5 mcg and Placebo	Tiotropium 5 mcg and Placebo	Tiotropium 18 mcg and Placebo
STARTED	5741	5729	5713
COMPLETED	4400 ^[1]	4399 ^[1]	4400 ^[1]
NOT COMPLETED	1341	1330	1313
Not treated	11	18	19
Sites with data irregularities/fraud	6	6	7
Adverse Event	602	606	635
Lack of Efficacy	65	60	59
Protocol Violation	64	66	41
Lost to Follow-up	52	63	55
Withdrawal by Subject	331	335	319
Other reason not specified	210	176	178

[1]	See Pre-Assignment Details above for comments.

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): This analysis set included all randomized subjects without data irregularities who were documented to have taken at least one dose of investigational treatment.

Reporting Groups

	Description
Tiotropium 2.5 mcg and Placebo	Patients receive one of the active tiotropium arms daily tiotropium 1.25 mcg (2 actuations/day): soft mist inhaler 2 actuations=2 puffs/day
Tiotropium 5 mcg and Placebo	Patients receive one of the active tiotropium arms daily tiotropium 2.5 mcg (2 actuations/day): soft mist inhaler (2 actuations=2 puffs/day)
Tiotropium 18 mcg and Placebo	Patients receive one of the active tiotropium arms daily tiotropium 18 mcg: HandiHaler
Total	Total of all reporting groups

Baseline Measures

	Tiotropium 2.5 mcg and Placebo	Tiotropium 5 mcg and Placebo	Tiotropium 18 mcg and Placebo	Total
Number of Participants [units: participants]	5724	5705	5687	17116
Age [units: years] Mean ± Standard Deviation	65.1 ± 9.1	64.9 ± 9.1	65.0 ± 9.0	65.0 ± 9.1
Gender [units: participants]
Female	1656	1571	1652	4879
Male	4068	4134	4035	12237

Outcome Measures

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1. Primary:

Time to All-Cause Mortality [ Time Frame: Up to 3 years ]

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2. Primary:

Time to First COPD Exacerbation [ Time Frame: Up to 3 years ]

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3. Secondary:

Trough FEV1 Over 120 Weeks (in a Substudy of 1370 Patients) [ Time Frame: Up to 3 years ]

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4. Secondary:

Number of COPD Exacerbations [ Time Frame: Up to 3 years ]

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5. Secondary:

Time to First Hospitalization Associated With COPD Exacerbation [ Time Frame: Up to 3 years ]

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6. Secondary:

Number of Hospitalizations Associated With COPD Exacerbation [ Time Frame: Up to 3 years ]

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7. Secondary:

Time to First Moderate to Severe COPD Exacerbation [ Time Frame: Up to 3 years ]

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8. Secondary:

Time to Onset of First Major Adverse Cardiovascular Event (MACE) [ Time Frame: Up to 3 years ]

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9. Secondary:

Time to Death From Major Adverse Cardiovascular Event (MACE) [ Time Frame: Up to 3 years ]

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Serious Adverse Events

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Other Adverse Events

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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
Prospectively defined outcome events, serious adverse events, adverse events leading to discontinuation, and investigator-determined drug-related adverse events were required for collection in this trial.

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.

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:

Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, Dusser D, Joseph E, Kattenbeck S, Koenen-Bergmann M, Pledger G, Calverley P; TIOSPIR Investigators. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013 Oct 17;369(16):1491-501. doi: 10.1056/NEJMoa1303342. Epub 2013 Aug 30.

Responsible Party:	Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT01126437 History of Changes
Other Study ID Numbers:	205.452, 2009-015713-51
Study First Received:	May 6, 2010
Results First Received:	May 20, 2014
Last Updated:	May 20, 2014
Health Authority:	Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica Australia: Dept of Health and Ageing Therapeutic Goods Admin Austria: Medicines and Medical Devices Agency Belgium: Federal Agency for Medicinal and Health Products Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency Canada: Health Canada China: Food and Drug Administration Columbia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos Croatia: Agency for Medicinal Product and Medical Devices Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Georgia: Ministry of Health Germany: Federal Institute for Drugs and Medical Devices Greece: Ethics Committee Guatemala: Ministry of Public Health and Social Assistance Hungary: National Institute of Pharmacy India: Drugs Controller General of India Ireland: Irish Medicines Board Israel: Israeli Health Ministry Pharmaceutical Administration Italy: Ethics Committee Latvia: State Agency of Medicines Lithuania: State Medicine Control Agency - Ministry of Health Malaysia: Ministry of Health Mexico: Federal Commission for Sanitary Risks Protection Netherlands: Central Committee Research Involving Human Subjects New Zealand: Multi-Regional Ethics Committee Norway: Norwegian Medicines Agency Panama: Ministry of Health Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Philippines: Bureau of Food and Drugs Poland: Registration Medicinal Product Medical Device Biocidal Product Portugal: National Pharmacy and Medicines Institute Romania: National Medicines Agency Russia: Pharmacological Committee, Ministry of Health Serbia and Montenegro: Agency for Drugs and Medicinal Devices Slovakia: State Institute for Drug Control South Africa: Medicines Control Council South Korea: Ministry of Food and Drug Safety (MFDS) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency Switzerland: Swissmedic Taiwan: Department of Health Thailand: Food and Drug Administration Tunisia: Ministry of Public Health Turkey: Ministry of Health Ukraine: State Pharmacological Center - Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

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