Efficacy and Safety of Indacaterol Plus Tiotropium Versus... | NCT00877383

NCT00877383

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Indacaterol 150 μg and tiotropium 18 μg	Experimental	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol 150 μg Drug: Tiotropium 18 μg
Tiotropium 18 μg	Active Comparator	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.	Drug: Tiotropium 18 μg Drug: Placebo to indacaterol

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Indacaterol 150 μg	Drug	Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.	Indacaterol 150 μg and tiotropium 18 μg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 the Study (Week 12, Day 84)	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). The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. 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.	From 5 minutes to 8 hours post-dose at the end of the study (Week 12, Day 84)

Secondary Outcomes

Measure	Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study. 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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigator Site		Anniston	Alabama	36207-5710	United States
Novartis Investigator Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22544891	Derived	Mahler DA, D'Urzo A, Bateman ED, Ozkan SA, White T, Peckitt C, Lassen C, Kramer B; INTRUST-1 and INTRUST-2 study investigators. Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax. 2012 Sep;67(9):781-8. doi: 10.1136/thoraxjnl-2011-201140. Epub 2012 Apr 27.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
BG001	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0001.46± 0.011 OG0011.34± 0.011

Secondary

Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)

FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study. 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.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

End of the study (Week 12 + 1 day, Day 85)

ID	Title	Description
OG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Secondary

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. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. 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.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 8 hours post-dose on Day 1

ID	Title	Description
OG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg

Secondary

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. Trough FEV1 was defined as the average of measurements made 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.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

24 hours post-dose on Day 2

ID	Title	Description
OG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Secondary

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. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. 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.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 4 hours post-dose on Day 1

ID	Title	Description
OG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg

Secondary

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 the Study (Week 12, Day 84)

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 the study (Week 12, Day 84). The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. 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.

Full analysis set (FAS): All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).

Posted

Least Squares Mean

Standard Error

Liters

From 5 minutes to 4 hours post-dose at the end of the study (Week 12, Day 84)

ID	Title	Description
OG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
OG001	Tiotropium 18 μg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.			19	572	83	572
EG001	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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.			18	570	70	570

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Cardiac arrest	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Hypertensive heart disease	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0011 affected570 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Colonic polyp	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Oesophageal spasm	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0011 affected570 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected572 at risk EG0011 affected570 at risk
Lower respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected572 at risk EG0010 affected570 at risk
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Upper respiratory tract infection bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Fractured coccyx	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Post procedural myocardial infarction	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Lung squamous cell carcinoma stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0009 affected572 at risk EG0019 affected570 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0011 affected570 at risk
Aortic aneurysm	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Arteriosclerosis	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected572 at risk EG0012 affected570 at risk
Hypotension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected572 at risk EG0010 affected570 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG00038 affected572 at risk EG00152 affected570 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG00052 affected572 at risk EG00125 affected570 at risk

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 β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D000470	Alkaloids
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring