Efficacy and Safety of Indacaterol Plus Tiotropium Versus Tiotropium Alone in Patients With Chronic Obstructive Pulmonary Disease
INTRUST1
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
1 other identifier
interventional
1,134
12 countries
137
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2009
Shorter than P25 for phase_3
137 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2009
CompletedFirst Posted
Study publicly available on registry
February 18, 2009
CompletedStudy Start
First participant enrolled
March 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2010
CompletedResults Posted
Study results publicly available
August 18, 2011
CompletedAugust 18, 2011
July 1, 2011
1 year
February 15, 2009
July 22, 2011
July 22, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
From 5 minutes to 8 hours post-dose at the end of treatment (Week 12, Day 84)
Secondary Outcomes (5)
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85)
24 hours post-dose at the end of treatment (Week 12 + 1 day, Day 85)
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
From 5 minutes to 8 hours post-dose on Day 1
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2
24 hours post-dose on Day 2
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
From 5 minutes to 4 hours post-dose on Day 1
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)
From 5 minutes to 4 hours post-dose at the end of treatment (Week 12)
Study Arms (2)
Indacaterol 150 μg and tiotropium 18 μg
EXPERIMENTALPatients 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.
Tiotropium 18 μg
ACTIVE COMPARATORPatients 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.
Interventions
Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
Tiotropium was supplied in powder filled capsules together the manufacture's proprietary inhalation device (HandiHaler®).
Placebo to indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
Eligibility Criteria
You may qualify if:
- 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:
- Smoking history of at least 10 pack-years
- Post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤ 65% and ≥ 30% of the predicted normal value
- Post-bronchodilator FEV1/FVC (force vital capacity) \< 70%
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (137)
Novartis Investigator Site
Birmingham, Alabama, 32509, United States
Novartis Investigator Site
Mobile, Alabama, 36608, United States
Novartis Investigative Site
Scottsdale, Arizona, 85258, United States
Novartis Investigative Site
Tucson, Arizona, 85712, United States
Novartis Investigative Site
Tucson, Arizona, 85723, United States
Novartis Investigator Site
Pine Bluff, Arkansas, 71603, United States
Novartis Investigator Site
Fountain Valley, California, 92708, United States
Novartis Investigator Site
Long Beach, California, 90822, United States
Novartis Investigative Site
Los Angeles, California, 90095, United States
Novartis Investigator Site
National City, California, 91950, United States
Novartis Investigator Site
Palmdale, California, 93551, United States
Novartis Investigative Site
Stockton, California, 95207, United States
Novartis Investigator Site
Temecula, California, 92591, United States
Novartis Investigative Site
Hartford, Connecticut, 06105-1208, United States
Novartis Investigative Site
Clearwater, Florida, 33756, United States
Novartis Investigator Site
Fort Walton Beach, Florida, 32547, United States
Novartis Investigative Site
Miami, Florida, 33136, United States
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Miami, Florida, 331577, United States
Novartis Investigative Site
Naranja, Florida, 33032, United States
Novartis Investigator Site
Pensacola, Florida, 32514, United States
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Sarasota, Florida, 34233, United States
Novartis Investigative Site
Atlanta, Georgia, 30342, United States
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Conyers, Georgia, 30094, United States
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Normal, Illinois, 61761, United States
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Iowa City, Iowa, 52240, United States
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Kansas City, Kansas, 66160, United States
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Lenexa, Kansas, 66215, United States
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Topeka, Kansas, 66606, United States
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Lafayette, Louisiana, 70503, United States
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Metaire, Louisiana, 70002, United States
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New Orleans, Louisiana, 70119, United States
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Slidell, Louisiana, 70458, United States
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Columbia, Maryland, 21044, United States
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Brockton, Massachusetts, 02301, United States
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Clarkston, Michigan, 48346, United States
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Detroit, Michigan, 48202, United States
Novartis Investigative Site
Saint Charles, Missouri, 63301, United States
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Missoula, Montana, 59808, United States
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Boys Town, Nebraska, 68010, United States
Novartis Investigative Site
Omaha, Nebraska, 68114, United States
Novartis Investigative site
Omaha, Nebraska, 68134, United States
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Las Vegas, Nevada, 89119, United States
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Lebanon, New Hampshire, 03756, United States
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Asbury Park, New Jersey, 07712, United States
Novartis Investigative Site
Rochester, New York, 14618, United States
Novartis Investigator Site
Mooresville, North Carolina, 28117, United States
Novartis Investigative Site
Winston-Salem, North Carolina, 27103, United States
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Tulsa, Oklahoma, 74135-2920, United States
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Medford, Oregon, 97504, United States
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Bethlehem, Pennsylvania, 18020, United States
Novartis Investigative Site
Cumberland, Rhode Island, 02864, United States
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Greenville, South Carolina, 29615, United States
Novartis Investigative Site
Spartanburg, South Carolina, 29303, United States
Novartis Investigator Site
Knoxville, Tennessee, 37919, United States
Novartis Investigator Site
El Paso, Texas, 79903, United States
Novartis Investigative Site
Houston, Texas, 77024, United States
Novartis Investigative Site
Houston, Texas, 77079, United States
Novartis Investigative Center
New Braunfels, Texas, 78130-6113, United States
Novartis Investigator Site
Newport News, Virginia, 23606, United States
Novartis Investigative Site
Richmond, Virginia, 23225, United States
Novartis Investigator Site
Richmond, Virginia, 23249, United States
Novartis Investigative Site
Buenos Aires, Argentina
Novartis Investigative Site
Corrientes, Argentina
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Córdoba, Argentina
Novartis Investigative SIte
Mendoza, Argentina
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Rosario, Argentina
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Box Hill, Australia
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Clayton, Australia
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Garran, Australia
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Glebe, Australia
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Kogarah, Australia
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Nedlands, Australia
Novartis Investigative Site
Barranquilla, Colombia
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Bogotá, Colombia
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Bogotá, Colombia
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Medellín, Colombia
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Copenhagen, Denmark
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Fredericia, Denmark
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Silkeborg, Denmark
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Soeborg, Denmark
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Vejle, Denmark
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Berlin, Germany
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Cottbus, Germany
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Donaustauf, Germany
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Dortmund, Germany
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Erfurt, Germany
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Frankfurt, Germany
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Gelnhausen, Germany
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Großhansdorf, Germany
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Hanover, Germany
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Heidelberg, Germany
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Leipzig, Germany
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Mainz, Germany
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Neu-Ulm, Germany
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Neuss, Germany
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Potsdam, Germany
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Rostock, Germany
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Schwabach, Germany
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Schwetzingen, Germany
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Straußberg, Germany
Novartis Investigative Site
Wiesbaden, Germany
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Wuppertal, Germany
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Guatemala City, Guatemala
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Guadalajara, Mexico
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Mexico City, Mexico
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Monterrey, Mexico
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Zapopan, Mexico
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Manila, Philippines
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Cape Town, South Africa
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eManzimtoti, South Africa
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eMkhomazi, South Africa
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Johannesburg, South Africa
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Midrand, South Africa
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A Coruña, Spain
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Alicante, Spain
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Barcelona, Spain
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Begonte, Spain
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Cadiz, Spain
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Granollers, Spain
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Jaén, Spain
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León, Spain
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Madrid, Spain
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Pamplona, Spain
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Torrelavega, Spain
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Valencia, Spain
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Vigo, Spain
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Antalya, Turkey (Türkiye)
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Çanakkale, Turkey (Türkiye)
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Isparta, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Kartal, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Kozlu / Zonguldak, Turkey (Türkiye)
Novartis Investigator Site
Malatya, Turkey (Türkiye)
Novartis Investigator Site
Manisa, Turkey (Türkiye)
Novartis Investigator Site
Mecidiyekoy/Istanbul, Turkey (Türkiye)
Novartis Investigator Site
Yenisehir/Izmir, Turkey (Türkiye)
Related Publications (1)
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.
PMID: 22544891DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
February 15, 2009
First Posted
February 18, 2009
Study Start
March 1, 2009
Primary Completion
March 1, 2010
Study Completion
March 1, 2010
Last Updated
August 18, 2011
Results First Posted
August 18, 2011
Record last verified: 2011-07