AsthmaPhase 3NCT00776984
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 II)
A Phase 3 study testing tiotropium 5mcg/day in people with Asthma, run by Boehringer Ingelheim at 75 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- tiotropium 5mcg/day
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 453 participants
- Where
- 75 sitesin 15 countries
- Study dates
- Oct 2008to Jul 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
- Male or female patients aged at least 18 years but not more than 75 years.
- All patients must have at least a 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.
- All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent
- All patients must have a history of one or more asthma exacerbation in the past year.
- Patients must have evidence of treated, severe, persistent asthma in postbronchodilator pulmonary function tests.
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- Patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment and who have a smoking history of less than 10 pack years
- Patients must be able to use the Respimat® inhaler correctly
- Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the electronic diary/peak flow meter.
Who cannot join
- Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient´s ability to participate in the trial.
- Patients with clinically relevant abnormal screening haematology or blood chemistry.
- Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.
- Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
- Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.
- Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
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- Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.
- Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.
- Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.
- Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.
- Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.
- Patients with a known narrow-angle glaucoma.
- Note:
- As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.
- As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of <= 50 mL/min) treated with tiotropium should be monitored closely.
Trial locations and contacts
75 sites in 15 countries.
75 sites in 15 countries
United States18 sites
205.417.01062 Boehringer Ingelheim Investigational Site
Albany, New York
205.417.01070 Boehringer Ingelheim Investigational Site
Canton, Ohio
205.417.01059 Boehringer Ingelheim Investigational Site
Chicago, Illinois
205.417.01061 Boehringer Ingelheim Investigational Site
Fountain Valley, California
205.417.01052 Boehringer Ingelheim Investigational Site
Fresno, California
205.417.01058 Boehringer Ingelheim Investigational Site
Great Neck, New York
205.417.01067 Boehringer Ingelheim Investigational Site
High Point, North Carolina
205.417.01063 Boehringer Ingelheim Investigational Site
Louisville, Kentucky
205.417.01064 Boehringer Ingelheim Investigational Site
New Orleans, Louisiana
205.417.01068 Boehringer Ingelheim Investigational Site
Normal, Illinois
205.417.01069 Boehringer Ingelheim Investigational Site
Ocean City, New Jersey
205.417.01066 Boehringer Ingelheim Investigational Site
Omaha, Nebraska
205.417.01065 Boehringer Ingelheim Investigational Site
Pensacola, Florida
205.417.01054 Boehringer Ingelheim Investigational Site
Richmond, Virginia
205.417.01055 Boehringer Ingelheim Investigational Site
Rockville Centre, New York
205.417.01051 Boehringer Ingelheim Investigational Site
Stockton, California
205.417.01053 Boehringer Ingelheim Investigational Site
Upland, Pennsylvania
205.417.01056 Boehringer Ingelheim Investigational Site
Waterbury, Connecticut
Japan16 sites
205.417.81063 Boehringer Ingelheim Investigational Site
Himeji, Hyogo
205.417.81056 Boehringer Ingelheim Investigational Site
Hiroshima, Hiroshima
205.417.81051 Boehringer Ingelheim Investigational Site
Itabashi-ku, Tokyo
205.417.81059 Boehringer Ingelheim Investigational Site
Kagoshima, Kagoshima
205.417.81053 Boehringer Ingelheim Investigational Site
Kishiwada, Osaka
205.417.81057 Boehringer Ingelheim Investigational Site
Kitakyusyu, Fukuoka
205.417.81058 Boehringer Ingelheim Investigational Site
Koga, Fukuoka
205.417.81055 Boehringer Ingelheim Investigational Site
Kurashiki, Okayama
205.417.81064 Boehringer Ingelheim Investigational Site
Kurume, Fukuoka
205.417.81062 Boehringer Ingelheim Investigational Site
Morioka, Iwate
205.417.81052 Boehringer Ingelheim Investigational Site
Osaka-sayama, Osaka
205.417.81066 Boehringer Ingelheim Investigational Site
Sendai, Miyagi
205.417.81065 Boehringer Ingelheim Investigational Site
Seto, Aichi
205.417.81060 Boehringer Ingelheim Investigational Site
Urasoe, Okinawa
205.417.81061 Boehringer Ingelheim Investigational Site
Urasoe, Okinawa
205.417.81054 Boehringer Ingelheim Investigational Site
Wakayama, Wakayama
Germany5 sites
205.417.49052 Boehringer Ingelheim Investigational Site
Berlin
205.417.49054 Boehringer Ingelheim Investigational Site
Hamburg
205.417.49053 Boehringer Ingelheim Investigational Site
Lübeck
205.417.49051 Boehringer Ingelheim Investigational Site
Rüdersdorf
205.417.49055 Boehringer Ingelheim Investigational Site
Weinheim
Italy4 sites
205.417.39052 Boehringer Ingelheim Investigational Site
Bussolengo (vr)
205.417.39054 Boehringer Ingelheim Investigational Site
Milan
205.417.39051 Boehringer Ingelheim Investigational Site
Pavia
205.417.39053 Boehringer Ingelheim Investigational Site
Pietra Ligure (sv)
New Zealand4 sites
205.417.64054 Boehringer Ingelheim Investigational Site
Auckland NZ
205.417.64053 Boehringer Ingelheim Investigational Site
Christchurch
205.417.64052 Boehringer Ingelheim Investigational Site
Newtown Wellington NZ
205.417.64051 Boehringer Ingelheim Investigational Site
Tauranga
South Africa4 sites
205.417.27051 Boehringer Ingelheim Investigational Site
Bellville
205.417.27052 Boehringer Ingelheim Investigational Site
Cape Town
205.417.27053 Boehringer Ingelheim Investigational Site
Cape Town
205.417.27054 Boehringer Ingelheim Investigational Site
Cape Town
Canada3 sites
205.417.02051 Boehringer Ingelheim Investigational Site
Mississauga, Ontario
205.417.02052 Boehringer Ingelheim Investigational Site
Montreal, Quebec
205.417.02053 Boehringer Ingelheim Investigational Site
Ottawa, Ontario
Netherlands3 sites
205.417.31051 Boehringer Ingelheim Investigational Site
Groningen
205.417.31053 Boehringer Ingelheim Investigational Site
Leeuwarden
205.417.31052 Boehringer Ingelheim Investigational Site
Schiedam
Russia3 sites
205.417.07051 Boehringer Ingelheim Investigational Site
Saint Petersburg
205.417.07052 Boehringer Ingelheim Investigational Site
Saint Petersburg
205.417.07053 Boehringer Ingelheim Investigational Site
Saint Petersburg
Serbia3 sites
205.417.38153 Boehringer Ingelheim Investigational Site
Belgrade
205.417.38152 Boehringer Ingelheim Investigational Site
Kamenitz
205.417.38151 Boehringer Ingelheim Investigational Site
Niš
Turkey (Türkiye)3 sites
205.417.90052 Boehringer Ingelheim Investigational Site
Ankara
205.417.90053 Boehringer Ingelheim Investigational Site
Ankara
205.417.90051 Boehringer Ingelheim Investigational Site
İzmit
Ukraine3 sites
205.417.38053 Boehringer Ingelheim Investigational Site
Kharkiv
205.417.38051 Boehringer Ingelheim Investigational Site
Kiev
205.417.38052 Boehringer Ingelheim Investigational Site
Vinnytsia
United Kingdom3 sites
205.417.44051 Boehringer Ingelheim Investigational Site
Chertsey
205.417.44053 Boehringer Ingelheim Investigational Site
Exeter
205.417.44052 Boehringer Ingelheim Investigational Site
Windsor
Denmark2 sites
205.417.45052 Boehringer Ingelheim Investigational Site
Aalborg
205.417.45051 Boehringer Ingelheim Investigational Site
Aarhus C
Australia1 site
205.417.61051 Boehringer Ingelheim Investigational Site
Concord, New South Wales
About this study
Official title: A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (5 mcg/Day) Over 48 Weeks as add-on Controller Therapy on Top of Usual Care in Patients With Severe Persistent Asthma
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.
- Conditions
- Asthma
- Being tested
- tiotropium 5mcg/day, placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tiotropium 5mcg/dayDrug
Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution
placeboDrug
Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution
| Study group | Role | What they receive |
|---|---|---|
| tiotropium 5mcg/day | Experimental | patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution Receives: Drug: tiotropium 5mcg/day |
| placebo | Experimental | patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 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.
Measured: Baseline and 24 weeks
Trough FEV1 Response Determined After a Treatment Period of 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.
Measured: Baseline and 24 weeks
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).
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.
Measured: 48 weeks
Secondary outcomes (29)
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.
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.
Measured: Baseline and 24 weeks
Trough FVC Response at the End of the 24-week Treatment Period.
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.
Measured: Baseline and 24 weeks
FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.
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.
Measured: Baseline and 24 weeks
FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.
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.
Measured: Baseline and 24 weeks
Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
Trough FEV1 Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
AUC0-3h FEV1 Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
Peak FVC 0-3h Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
Trough FVC Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
FVC AUC0-3h Response at the End of the 48-week Treatment Period.
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.
Measured: Baseline and 48 weeks
Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of 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.
Measured: Baseline and last 7 days before week 24 visit
Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of 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.
Measured: Baseline and last 7 days before week 24 visit
Mean Pre-dose FEV1 a.m. Response (Diary Data) of 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.
Measured: Baseline and last 7 days before week 24 visit
Mean Pre-dose FEV1-p.m.Response (Diary Data) of 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.
Measured: Baseline and last 7 days before week 24 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.
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.
Measured: Baseline and last 7 days before week 24 visit
Time to First Severe Asthma Exacerbation During the 48-week Treatment.
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.
Measured: 48 weeks
Number of Asthma Exacerbations Per Patient During the 48-week Treatment Period.
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.
Measured: 48 weeks
Number of Severe Asthma Exacerbations Per Patient During the 48-week Treatment Period.
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.
Measured: 48 weeks
Number of Patients With at Least One Asthma Exacerbation During the 48-week Treatment Period.
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.
Measured: 48 weeks
Number of Patients With at Least One Severe Asthma Exacerbation During the 48-week Treatment Period.
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.
Measured: 48 weeks
Time to First Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
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.
Measured: 48 weeks
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Measured: 48 weeks
Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
Measured: 48 weeks
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period.
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.
Measured: 24 weeks
AQLQ(S) Total Score at the End of the 48-week Treatment Period.
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.
Measured: 48 weeks
Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period.
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.
Measured: 24 weeks
ACQ Score at the End of the 48-week Treatment Period.
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.
Measured: 48 weeks
Asthma Symptom Free Days Response During the 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.
Measured: Baseline and last 7 days before week 24 visit
Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the 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.
Measured: Baseline and last 7 days before week 24 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 453 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00776984
- Sponsor's protocol ID
- 205.417
- Other IDs
- 2008-001414-25, 2008
- Status last verified
- Sep 2014
- First submitted
- 13 Oct 2008
- Last updated
- 10 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.
PubMed 36472162Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6.
PubMed 31319851Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, Moroni-Zentgraf P, Kerstjens HAM. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22.
PubMed 29174062Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.
PubMed 22938706
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (5 mcg/Day) Over 48 Weeks as add-on Controller Therapy on Top of Usual Care in Patients With Severe Persistent Asthma
- ClinicalTrials.gov ID
- NCT00776984
- Acronym / sponsor ID
- 205.417
- Conditions
- Asthma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 453 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- Oct 2008
- Primary completion
- Jul 2011 (actual)
- First posted
- 22 Oct 2008 (estimated)
- Results
- Posted 27 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tiotropium 5mcg/day | Experimental | Drug: tiotropium 5mcg/daypatient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution |
| placebo | Experimental | Drug: placebopatient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
- Male or female patients aged at least 18 years but not more than 75 years.
- All patients must have at least a 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.
- All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent
- All patients must have a history of one or more asthma exacerbation in the past year.
Key exclusion criteria (15 listed)
- Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient´s ability to participate in the trial.
- Patients with clinically relevant abnormal screening haematology or blood chemistry.
- Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.
- Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
- Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tiotropium 5mcg/dayIntervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution | Drug | tiotropium 5mcg/day |
| placeboIntervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution | Drug | placebo |
Primary outcome
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks.
Time frame: 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.
Trough FEV1 Response Determined After a Treatment Period of 24 Weeks.
Time frame: 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.
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).
Time frame: 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.
29 secondary outcomes
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.
Time frame: Baseline and 24 weeks
Trough FVC Response at the End of the 24-week Treatment Period.
Time frame: Baseline and 24 weeks
FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.
Time frame: Baseline and 24 weeks
FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.
Time frame: Baseline and 24 weeks
Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
Trough FEV1 Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
AUC0-3h FEV1 Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
Peak FVC 0-3h Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
Trough FVC Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
FVC AUC0-3h Response at the End of the 48-week Treatment Period.
Time frame: Baseline and 48 weeks
Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of Last-7-days-before-week-24-visit .
Time frame: Baseline and last 7 days before week 24 visit
Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of Last-7-days-before-week 24-visit.
Time frame: Baseline and last 7 days before week 24 visit
Mean Pre-dose FEV1 a.m. Response (Diary Data) of Last-7-days-before-week 24-visit.
Time frame: Baseline and last 7 days before week 24 visit
Mean Pre-dose FEV1-p.m.Response (Diary Data) of Last-7-days-before-week 24-visit.
Time frame: Baseline and last 7 days before week 24 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.
Time frame: Baseline and last 7 days before week 24 visit
Time to First Severe Asthma Exacerbation During the 48-week Treatment.
Time frame: 48 weeks
Number of Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Time frame: 48 weeks
Number of Severe Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Time frame: 48 weeks
Number of Patients With at Least One Asthma Exacerbation During the 48-week Treatment Period.
Time frame: 48 weeks
Number of Patients With at Least One Severe Asthma Exacerbation During the 48-week Treatment Period.
Time frame: 48 weeks
Time to First Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
Time frame: 48 weeks
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Time frame: 48 weeks
Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
Time frame: 48 weeks
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period.
Time frame: 24 weeks
AQLQ(S) Total Score at the End of the 48-week Treatment Period.
Time frame: 48 weeks
Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period.
Time frame: 24 weeks
ACQ Score at the End of the 48-week Treatment Period.
Time frame: 48 weeks
Asthma Symptom Free Days Response During the Last-7-days-before-week-24-visit .
Time frame: Baseline and last 7 days before week 24 visit
Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the Last-7-days-before-week-24-visit .
Time frame: Baseline and last 7 days before week 24 visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36472162Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.
- Derived from this study: PubMed 31319851Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6.
- Derived from this study: PubMed 29174062Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, Moroni-Zentgraf P, Kerstjens HAM. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22.
- Derived from this study: PubMed 22938706Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
75 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tiotropium 5mcg/day in people with Asthma, run by Boehringer Ingelheim at 75 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Japan, Germany, Italy, New Zealand and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks. (time frame: Baseline and 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00776984, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2014.