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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00846586




Registration number
NCT00846586
Ethics application status
Date submitted
15/02/2009
Date registered
18/02/2009
Date last updated
18/08/2011

Titles & IDs
Public title
Efficacy and Safety of Indacaterol Plus Tiotropium Versus Tiotropium Alone in Patients With Chronic Obstructive Pulmonary Disease
Scientific title
A Randomized, Double-blind, Controlled, Parallel-group, 12-week Study to Compare the Efficacy and Safety of the Combination of Indacaterol 150 µg Once Daily With Open Label Tiotropium 18 µg Once Daily Versus Open Label Tiotropium 18 µg Once Daily in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease
Secondary ID [1] 0 0
CQAB149B2341
Universal Trial Number (UTN)
Trial acronym
INTRUST1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Indacaterol 150 µg
Treatment: Drugs - Tiotropium 18 µg
Treatment: Drugs - Placebo to indacaterol

Experimental: Indacaterol 150 µg and tiotropium 18 µg - Patients inhaled indacaterol 150 µg and tiotropium 18 µg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting ß2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Active Comparator: Tiotropium 18 µg - Patients inhaled placebo to indacaterol 150 µg and tiotropium 18 µg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single dose dry powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting ß2-agonist salbutamol/albuterol was available for rescue use throughout the study.


Treatment: Drugs: Indacaterol 150 µg
Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.

Treatment: Drugs: Tiotropium 18 µg
Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®).

Treatment: Drugs: Placebo to indacaterol
Placebo to indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose at the End of Treatment (Week 12) - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [1] 0 0
From 5 minutes to 8 hours post-dose at the end of treatment (Week 12, Day 84)
Secondary outcome [1] 0 0
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study (Week 12 + 1 day, Day 85). The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [1] 0 0
24 hours post-dose at the end of treatment (Week 12 + 1 day, Day 85)
Secondary outcome [2] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose on Day 1 - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [2] 0 0
From 5 minutes to 8 hours post-dose on Day 1
Secondary outcome [3] 0 0
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [3] 0 0
24 hours post-dose on Day 2
Secondary outcome [4] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose on Day 1 - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose on Day 1. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [4] 0 0
From 5 minutes to 4 hours post-dose on Day 1
Secondary outcome [5] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of Treatment (Week 12) - FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose at the end of treatment (Week 12). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.
Timepoint [5] 0 0
From 5 minutes to 4 hours post-dose at the end of treatment (Week 12)

Eligibility
Key inclusion criteria
- Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate-to-severe as
classified by the Global Initiative for Chronic Obstructive Lung Disease [GOLD]
Guidelines, 2007) and:

1. Smoking history of at least 10 pack-years

2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) = 65% and = 30%
of the predicted normal value

3. Post-bronchodilator FEV1/FVC (force vital capacity) < 70%
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid
treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening or
during the run-in period

- Patients who have had a respiratory tract infection within 6 weeks prior to screening
or during the run-in period

- Patients with a body mass index less than 15 or more than 40 kg/m^2

- Patients with concomitant pulmonary disease

- Patients with a history of asthma

- Patients with diabetes Type I or uncontrolled diabetes Type II

- Any patient with lung cancer or a history of lung cancer

- Patients with a history of certain cardiovascular comorbid conditions

Other protocol-defined inclusion/exclusion criteria applied to the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigator Site - Box Hill
Recruitment hospital [2] 0 0
Novartis Investigator Site - Clayton
Recruitment hospital [3] 0 0
Novartis Investigator Site - Garran
Recruitment hospital [4] 0 0
Novartis Investigator Site - Glebe
Recruitment hospital [5] 0 0
Novartis Investigator Site - Kogarah
Recruitment hospital [6] 0 0
Novartis Investigator Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Box Hill
Recruitment postcode(s) [2] 0 0
- Clayton
Recruitment postcode(s) [3] 0 0
- Garran
Recruitment postcode(s) [4] 0 0
- Glebe
Recruitment postcode(s) [5] 0 0
- Kogarah
Recruitment postcode(s) [6] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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Arizona
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Arkansas
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California
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Connecticut
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Florida
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Georgia
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Illinois
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Iowa
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Kansas
Country [11] 0 0
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Louisiana
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Maryland
Country [13] 0 0
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State/province [13] 0 0
Massachusetts
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State/province [14] 0 0
Michigan
Country [15] 0 0
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Missouri
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Montana
Country [17] 0 0
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New York
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North Carolina
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Tennessee
Country [29] 0 0
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Texas
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United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
Argentina
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Buenos Aires
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Argentina
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Cordoba
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Argentina
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Corrientes
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Argentina
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Mendoza
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Argentina
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Rosario
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Colombia
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Barranquilla
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Colombia
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Bogota
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Colombia
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Medellin
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Denmark
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Copenhagen
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Fredericia
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Silkeborg
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Soeborg
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Denmark
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Vejle
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Germany
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Berlin
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Germany
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Cottbus
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Donaustauf
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Germany
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Dortmund
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Erfurt
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Germany
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Frankfurt
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Germany
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Gelnhausen
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Germany
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Grosshansdorf
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Hannover
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Heidelberg
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Leipzig
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Germany
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Mainz
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Neu-Ulm
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Neuss
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Potsdam
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Rostock
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Schwabach
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Schwetzingen
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Germany
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Straussberg
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Wiesbaden
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Germany
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Wuppertal
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Guatemala
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Guatemala City
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Guatemala
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Guatemala
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Mexico
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Guadalajara
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Mexico
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Mexico City
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Monterrey
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Zapopan
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Manila
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Amanzimtoti
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South Africa
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Cape Town
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Johannesburg
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Midrand
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Umkomaas
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Spain
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Alicante
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Barcelona
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Spain
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Begonte
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Cadiz
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Granollers
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Spain
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Jaén
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Spain
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La Coruna
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Spain
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Leon
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Torrelavega
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Spain
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Valencia
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Spain
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Vigo
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Turkey
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Antalya
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Turkey
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Canakkale
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Turkey
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Isparta
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Turkey
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Istanbul
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Turkey
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Kartal
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Turkey
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Kayseri
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Turkey
State/province [96] 0 0
Kozlu / Zonguldak
Country [97] 0 0
Turkey
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Malatya
Country [98] 0 0
Turkey
State/province [98] 0 0
Manisa
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Turkey
State/province [99] 0 0
Mecidiyekoy/Istanbul
Country [100] 0 0
Turkey
State/province [100] 0 0
Yenisehir/Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study assessed the efficacy and safety of indacaterol (150 µg once daily [od]) when
combined with tiotropium (18 µg od) versus tiotropium (18 µg od) treatment alone in patients
with chronic obstructive pulmonary disease (COPD)
Trial website
https://clinicaltrials.gov/show/NCT00846586
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications