Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I)
- Registration Number
- NCT00772538
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined as add-on controller therapy on top of usual care in patients with severe persistent asthma.
The primary objective of each trial is to evaluate the long term efficacy of tiotropium over placebo on top of usual care in patients with severe persistent asthma as determined by pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on asthma control and health care resource utilisation. The secondary objective of each trial is to compare the long term safety of tiotropium with placebo in this patient population.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 459
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium 5mcg/day tiotropium 5mcg/day patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution placebo placebo patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution
- Primary Outcome Measures
Name Time Method Trough FEV1 Response Determined After a Treatment Period of 24 Weeks. Baseline and 24 weeks The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 24 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks. Baseline and 24 weeks Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Time to First Severe Asthma Exacerbation During the 48-week Treatment of the Pooled Data From the Two Twin Trials 205.416 (NCT00772538) and the Present 205.417 (NCT00776984). 48 weeks Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.
- Secondary Outcome Measures
Name Time Method FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period. Baseline and 24 weeks The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.
Mean Pre-dose FEV1 a.m. Response (Diary Data) of Last-7-days-before-week 24-visit. Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Mean Pre-dose FEV1-p.m.Response (Diary Data) of Last-7-days-before-week 24-visit. Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Time to First Severe Asthma Exacerbation During the 48-week Treatment. 48 weeks Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.
Time to First Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period. 48 weeks Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.
ACQ at the End of the 48-week Treatment Period. 48 weeks For the ACQ, the total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Asthma Symptom Free Days Response During the Last-7-days-before-week-24-visit . Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The response is defined as the change of the weekly mean from the baseline weekly mean. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Trough FVC Response at the End of the 24-week Treatment Period. Baseline and 24 weeks The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 24 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
FVC (AUC0-3h) Response at the End of the 24-week Treatment Period. Baseline and 24 weeks The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.
AUC0-3h FEV1 Response at the End of the 48-week Treatment Period. Baseline and 48 weeks The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.
Number of Asthma Exacerbations Per Patient During the 48-week Treatment Period. 48 weeks Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.
Number of Patients With at Least One Asthma Exacerbation During the 48-week Treatment Period. 48 weeks Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period. 48 weeks Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period. 48 weeks AQLQ(S) Total Score at the End of the 48-week Treatment Period. 48 weeks The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period. 24 weeks For the ACQ, the total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Peak FEV1 0-3h Response at the End of the 48-week Treatment Period. Baseline and 48 weeks Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Trough FEV1 Response at the End of the 48-week Treatment Period. Baseline and 48 weeks The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 48 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Mean PEF Variability Response (Absolute Difference Between Morning and Evening PEF Value Divided by Their Mean) of Last-7-days-before-week 24-visit. Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The PEF variability is the absolute difference between morning and evening PEF value divided by their mean, expressed as a percent. Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period. 24 weeks The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period. Baseline and 24 weeks Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Peak FVC 0-3h Response at the End of the 48-week Treatment Period. Baseline and 48 weeks Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Trough FVC Response at the End of the 48-week Treatment Period. Baseline and 48 weeks The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 48 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
FVC AUC0-3h Response at the End of the 48-week Treatment Period. Baseline and 48 weeks The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit baseline\*visit.
Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of Last-7-days-before-week-24-visit . Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of Last-7-days-before-week 24-visit. Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Number of Severe Asthma Exacerbations Per Patient During the 48-week Treatment Period. 48 weeks Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.
Number of Patients With at Least One Severe Asthma Exacerbation During the 48-week Treatment Period. 48 weeks Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.
Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the Last-7-days-before-week-24-visit . Baseline and last 7 days before week 24 visit Weekly means obtained during the last 7 days before week 24 visit were compared. The response is defined as the change of the weekly mean from the baseline weekly mean. The use of PRN salbutamol (albuterol rescue medication) is determined by the number of puffs of rescue therapy used per day. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.
Trial Locations
- Locations (73)
205.416.01014 Boehringer Ingelheim Investigational Site
🇺🇸Wheaton, Maryland, United States
205.416.49003 Boehringer Ingelheim Investigational Site
🇩🇪Gelnhausen, Germany
205.416.01008 Boehringer Ingelheim Investigational Site
🇺🇸San Diego, California, United States
205.416.01003 Boehringer Ingelheim Investigational Site
🇺🇸Lexington, Kentucky, United States
205.416.01024 Boehringer Ingelheim Investigational Site
🇺🇸Oklahoma City, Oklahoma, United States
205.416.45001 Boehringer Ingelheim Investigational Site
🇩🇰Hvidovre, Denmark
205.416.61002 Boehringer Ingelheim Investigational Site
🇦🇺Woodville, South Australia, Australia
205.416.81007 Boehringer Ingelheim Investigational Site
🇯🇵Hachioji, Tokyo, Japan
205.416.01007 Boehringer Ingelheim Investigational Site
🇺🇸Birmingham, Alabama, United States
205.416.01004 Boehringer Ingelheim Investigational Site
🇺🇸Walnut Creek, California, United States
205.416.01025 Boehringer Ingelheim Investigational Site
🇺🇸North Dartmouth, Massachusetts, United States
205.416.49005 Boehringer Ingelheim Investigational Site
🇩🇪Koblenz, Germany
205.416.27001 Boehringer Ingelheim Investigational Site
🇿🇦Cape Town, South Africa
205.416.01021 Boehringer Ingelheim Investigational Site
🇺🇸Boys Town, Nebraska, United States
205.416.39002 Boehringer Ingelheim Investigational Site
🇮🇹Sesto S. Giovanni (MI), Italy
205.416.90001 Boehringer Ingelheim Investigational Site
🇹🇷Istanbul, Turkey
205.416.44005 Boehringer Ingelheim Investigational Site
🇬🇧Nottingham, United Kingdom
205.416.02004 Boehringer Ingelheim Investigational Site
🇨🇦Quebec, Canada
205.416.61001 Boehringer Ingelheim Investigational Site
🇦🇺Daw Park, South Australia, Australia
205.416.81012 Boehringer Ingelheim Investigational Site
🇯🇵Maebashi, Gunma, Japan
205.416.81008 Boehringer Ingelheim Investigational Site
🇯🇵Minato-ku, Tokyo, Japan
205.416.27003 Boehringer Ingelheim Investigational Site
🇿🇦Durban, South Africa
205.416.49002 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.416.38103 Boehringer Ingelheim Investigational Site
🇷🇸Zemun, Serbia
205.416.81016 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
205.416.90002 Boehringer Ingelheim Investigational Site
🇹🇷Izmir, Turkey
205.416.27002 Boehringer Ingelheim Investigational Site
🇿🇦Durban, South Africa
205.416.44003 Boehringer Ingelheim Investigational Site
🇬🇧Brighton, United Kingdom
205.416.01012 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
205.416.01018 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
205.416.01016 Boehringer Ingelheim Investigational Site
🇺🇸Riverside, California, United States
205.416.01023 Boehringer Ingelheim Investigational Site
🇺🇸Tallahassee, Florida, United States
205.416.01022 Boehringer Ingelheim Investigational Site
🇺🇸Columbia, Missouri, United States
205.416.02001 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada
205.416.61003 Boehringer Ingelheim Investigational Site
🇦🇺Nedlands, Western Australia, Australia
205.416.45002 Boehringer Ingelheim Investigational Site
🇩🇰Odense C, Denmark
205.416.44002 Boehringer Ingelheim Investigational Site
🇬🇧Leicester, United Kingdom
205.416.44004 Boehringer Ingelheim Investigational Site
🇬🇧Nottingham, United Kingdom
205.416.81002 Boehringer Ingelheim Investigational Site
🇯🇵Sendai, Miyagi, Japan
205.416.81010 Boehringer Ingelheim Investigational Site
🇯🇵shinagawa-ku, Tokyo, Japan
205.416.01002 Boehringer Ingelheim Investigational Site
🇺🇸Elk Grove Village, Illinois, United States
205.416.01001 Boehringer Ingelheim Investigational Site
🇺🇸Cincinnati, Ohio, United States
205.416.01011 Boehringer Ingelheim Investigational Site
🇺🇸Cherry Hill, New Jersey, United States
205.416.01017 Boehringer Ingelheim Investigational Site
🇺🇸Lake Oswego, Oregon, United States
205.416.01019 Boehringer Ingelheim Investigational Site
🇺🇸El Paso, Texas, United States
205.416.39001 Boehringer Ingelheim Investigational Site
🇮🇹Pisa, Italy
205.416.49004 Boehringer Ingelheim Investigational Site
🇩🇪Oschersleben, Germany
205.416.07002 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.416.27004 Boehringer Ingelheim Investigational Site
🇿🇦Pretoria, South Africa
205.416.02003 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
205.416.81009 Boehringer Ingelheim Investigational Site
🇯🇵Minato-ku, Tokyo, Japan
205.416.81014 Boehringer Ingelheim Investigational Site
🇯🇵Noda, Chiba, Japan
205.416.81015 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
205.416.81011 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, Japan
205.416.31001 Boehringer Ingelheim Investigational Site
🇳🇱Groningen, Netherlands
205.416.31004 Boehringer Ingelheim Investigational Site
🇳🇱Helmond, Netherlands
205.416.38003 Boehringer Ingelheim Investigational Site
🇺🇦Vinnytsya, Ukraine
205.416.07001 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.416.81001 Boehringer Ingelheim Investigational Site
🇯🇵Naka-gun, Ibaraki, Japan
205.416.38102 Boehringer Ingelheim Investigational Site
🇷🇸Kragujevac, Serbia
205.416.38001 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine
205.416.01010 Boehringer Ingelheim Investigational Site
🇺🇸Stamford, Connecticut, United States
205.416.07003 Boehringer Ingelheim Investigational Site
🇷🇺Reutov - Moscow region, Russian Federation
205.416.38101 Boehringer Ingelheim Investigational Site
🇷🇸Belgrade, Serbia
205.416.02002 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
205.416.31005 Boehringer Ingelheim Investigational Site
🇳🇱Breda, Netherlands
205.416.31003 Boehringer Ingelheim Investigational Site
🇳🇱Zutphen, Netherlands
205.416.38002 Boehringer Ingelheim Investigational Site
🇺🇦Kharkov, Ukraine
205.416.81004 Boehringer Ingelheim Investigational Site
🇯🇵Inashiki-gun, Ibaraki, Japan
205.416.81006 Boehringer Ingelheim Investigational Site
🇯🇵Kamogawa, Chiba, Japan
205.416.81005 Boehringer Ingelheim Investigational Site
🇯🇵Tsukuba, Ibaraki, Japan
205.416.81003 Boehringer Ingelheim Investigational Site
🇯🇵Yonezawa, Yamagata, Japan
205.416.01009 Boehringer Ingelheim Investigational Site
🇺🇸Richmond, Virginia, United States