Pulmonary Disease, Chronic ObstructivePhase 4NCT02853123
Effect of Tiotropium + Olodaterol on Breathlessness in COPD Patients
A Phase 4 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 13 sites in 4 countries.
Trial summary
The primary objective of the present study is to evaluate the effect of tiotropium + olodaterol fixed dose combination (FDC) compared to tiotropium monotherapy on the intensity of breathlessness during the 3min constant speed shuttle test (CSST). Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Tiotropium and Olodaterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 13 sitesin 4 countries
- Study dates
- 22 Sep 2016to 14 Aug 2017
- Phase
- Phase 4
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice guidelines prior to participation in the trial, including medication washout and restrictions
- Diagnosis of Chronic Obstructive Pulmonary Disease and relatively stable airway obstruction: post bronchodilator 30%<= Forced Expiratory Volume in 1st second (FEV1)<80% of predicted normal (European Coal and Steel Community) and a post bronchodilator FEV1/Forced Vital Capacity<0.70 at visit 1
- Male or female patients >=40 and =<75 years of age on day of signing consent.
- Current or ex-smokers with a smoking history > 10 pack-years. Patients who have never smoked cigarettes must be excluded.
- Baseline Dyspnea Index score< 8 at visit 0.
- Hyperinflation at rest, defined as Functional Residual Capacity > 120% predicted at visit 1.
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- Borg dyspnea score >=4 at the end of 3min Constant Speed Shuttle Test at visit 2
- Perform technically acceptable pulmonary function tests (spirometry and body plethysmography) and complete multiple shuttle tests during the study period
- Inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler
Who cannot join
- Significant disease other than Chronic Obstructive Pulmonary Disease (COPD); a significant disease which, in the investigator's opinion, may (i) put the patient at risk (ii) influence the study results or (iii) cause concern regarding the patient's ability to participate
- Clinically relevant abnormal baseline haematology, blood chemistry, in the investigator's opinion, or creatinine >x2 Upper Limit Normal will be excluded regardless of clinical condition
- Current documented diagnosis of asthma
- COPD exacerbation in the 6 weeks prior to screening
- Diagnosis of thyrotoxicosis
- History of myocardial infarction within 6 months of screening
Show all 30Show fewer
- Life-threatening cardiac arrhythmia (investigator judgment)
- Known active tuberculosis
- Any malignancy unless free of disease for at least 5 years (treated basal cell carcinoma or squamous cell skin cancers are allowed)
- History of cystic fibrosis
- Clinically relevant bronchiectasis (investigator judgment)
- Severe emphysema requiring endobronchial interventions within 6 months prior to screening
- History of significant alcohol or drug abuse (investigator judgment)
- Any contraindications for exercise testing
- Patients who have undergone thoracotomy with pulmonary resection
- Treatment with any oral or patch ß-adrenergics
- Treatment with oral corticosteroid medication at unstable doses or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day
- Treatment with antibiotics for any reason within 4 weeks of screening
- Patients being treated with Phosphodiesterase Type 4 (PDE4) inhibitors within 3 months of screening visit should not be enrolled and PDE4 inhibitors should not be withdrawn for the purpose of enrolling in this study
- Regular use of daytime oxygen therapy for >1 hour per day and in the investigator's opinion will be unable to abstain from use during clinic visits
- Completion of a pulmonary rehabilitation program 6 weeks prior to screening or currently in a program
- Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea, such as arthritis in the leg, angina pectoris, claudication, morbid obesity
- Endurance time >=12 minutes during the incremental shuttle walk test
- Oxygen saturation < 85% (on room air) at rest or during exercise.
- Taken an investigational drug within 1 month or 6 half-lives or in case the investigational drug class is listed within the washout period specified prior to screening visit
- Known hypersensitivity to ß-adrenergics and/or anticholinergic drugs, Benzalkonium Chloride, Ethylenediaminetetraacetic acid or any other component of the Respimat® inhalation solution
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
- Women of childbearing potential not using a highly effective method of birth control
- Previously been randomized in this study or are currently participating in another study
- Unable to comply with pulmonary medication restrictions prior to randomization
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
Canada4 sites
McMaster Univ. Medical Centre
Hamilton, Ontario, L8N 3Z5
Kingston General Hospital
Kingston, Ontario, K7L 2V7
McGill University Health Centre (MUHC)
Montreal, Quebec, H4A 3J1
IUCPQ (Laval University)
Québec, G1V 4G5
Belgium3 sites
Genk - PRAC Janssens, E.
Genk, 3600
Hasselt - PRAC Aumann, J-L
Hasselt, 3500
UZ Leuven
Leuven, 3000
Germany3 sites
Klinische Forschung Berlin GbR
Berlin, 10787
IKF Pneumologie GmbH & Co. KG
Frankfurt am Main, 60596
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927
Netherlands3 sites
Catharina Ziekenhuis
Eindhoven, 5623 EJ
Zuyderland Medisch Centrum
Heerlen, 6419 PC
Gelre Ziekenhuis Zutphen
Zutphen, 7207 AE
About this study
Official title: A Randomised, Double-blind, Cross-over Study to Evaluate the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (5/5 µg) Compared With Tiotropium (5 µg), Both Delivered by the Respimat® Inhaler, on Breathlessness During the Three Minute Constant Speed Shuttle Test (3min CSST) in Patients With Chronic Obstructive Pulmonary Disease (COPD). [OTIVATO TM]
The primary objective of the present study is to evaluate the effect of tiotropium + olodaterol fixed dose combination (FDC) compared to tiotropium monotherapy on the intensity of breathlessness during the 3min constant speed shuttle test (CSST).
A secondary objective is to explore the relationship between reductions in breathlessness during the 3min CSST and reductions in breathlessness during activities of everyday living as measured by the dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) following bronchodilator therapy.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Tiotropium, Olodaterol
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiotropiumDrug
fixed dose combination once daily
OlodaterolDrug
fixed dose combination once daily
TiotropiumDrug
| Study group | Role | What they receive |
|---|---|---|
| Tiotropium + Olodaterol | Experimental | Patients will receive tiotropium 5mcg + olodaterol 5mcg in a fixed dose combination once daily. Receives: Drug: Tiotropium; Drug: Olodaterol |
| Tiotropium | Active comparator | Not described Receives: Drug: Tiotropium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Intensity of Breathlessness Measured Using the Modified Borg Scale at the End of the 3 Minute (Min) Constant Speed Shuttle Test After 6 Weeks of Treatment.
At 3 min or end of exercise (if 3 min not achieved), patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). The modified Borg scale is 10-point subjective scoring system, in which a patient rates effort of exertion while performing a particular activity. The scale is 0 to 10, the higher the score, the greater the perceived difficulty. Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Secondary outcomes (7)
Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured Prior to Exercise
Inspiratory Capacity (IC) is a standard measurement for the assessment of lung function. IC measurements were performed prior to the 3min Constant Speed Shuttle Test (CSST) (at rest). Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured at the End of Exercise
Inspiratory Capacity (IC) is a standard measurement for the assessment of lung function. IC measurements were performed at the end of the 3min Constant Speed Shuttle Test (CSST). Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Expiratory Volume
Forced Expiratory Volume in 1st second (FEV1) is a standard measurement for the assessment of lung function. The best of 3 efforts was defined as the highest FEV1, each obtained on any of 3 manoeuvres meeting the American Thoracic Society (ATS) criteria (to a maximum of 5 attempts). Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Vital Capacity
Forced Vital Capacity (FVC) is a standard measurement for the assessment of lung function. The best of 3 efforts was defined as the highest FVC, each obtained on any of 3 manoeuvres meeting the American Thoracic Society (ATS) criteria (to a maximum of 5 attempts). Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Intensity of Breathlessness (MBS-S) at 1, 2 and 2.5 Minute (Min) During the 3 Min Constant Speed Shuttle Test
At 1, 2 and 2.5 min during exercise, patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). At 3 min or end of exercise (if 3 min not achieved), patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). The modified Borg scale is 10-point subjective scoring system, in which a patient rates effort of exertion while performing a particular activity. The scale is 0 to 10, the higher the score, the greater the perceived difficulty. Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Individualized (CRQ-SAI) Dyspnoea Domain Score
CRQ-SAI refers to the CRQ-Self-administered individualized format as it contains a dyspnea domain that is individualized to each patient. This version was derived from the original CRQ tool \& therefore, is scored on 7-point Likert-type scale (1: maximum impairment to 7: no impairment) for each 4 domains covering: dyspnea, fatigue, emotional function \& mastery. Dyspnea items may be selected from list of 26 suggested items or written in by the patients. The patients are asked to select up to 5 activities associated with breathlessness that they perform frequently and are most important to them. The scores for each question of each domain were added together and divided by the number of questions answered in each domain. The higher scores indicate better health-related quality of life in the respective domain. Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) Dyspnoea Domain Score
CRQ-SAS was questionnaire to assess patients' perception of COPD and measures the impact of COPD on their life. This version was derived from the original CRQ tool \& therefore, is scored on 7-point Likert-type scale (1: maximum impairment to 7: no impairment) for each 4 domains covering: dyspnea, fatigue, emotional function \& mastery. The CRQ-SAS refers to the CRQ-Self-administered standardized format \& contains 20 questions. The first part of the questionnaire contains 5 standardized dyspnea questions and the patients must indicate how much shortness of breath they have experienced while performing each of these 5 activities. The scores for each question of each domain were added together and divided by the number of questions answered in each domain. The higher scores indicate better health-related quality of life in the respective domain. Measure type is actually Adjusted Mean Change from Baseline.
Measured: Baseline and week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2016 (estimated)
- Study start22 Sep 2016
- Primary completion24 Jul 2017
- Study completion14 Aug 2017
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.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02853123
- Sponsor's protocol ID
- 1237.28
- Other IDs
- 2015-002974-20, 2015
- Status last verified
- Aug 2019
- First submitted
- 29 Jul 2016
- Last updated
- 27 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Cross-over Study to Evaluate the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (5/5 µg) Compared With Tiotropium (5 µg), Both Delivered by the Respimat® Inhaler, on Breathlessness During the Three Minute Constant Speed Shuttle Test (3min CSST) in Patients With Chronic Obstructive Pulmonary Disease (COPD). [OTIVATO TM]
- ClinicalTrials.gov ID
- NCT02853123
- Acronym / sponsor ID
- 1237.28
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2016 (actual)
- Primary completion
- 24 Jul 2017 (actual)
- Study completion
- 14 Aug 2017 (actual)
- First posted
- 2 Aug 2016 (estimated)
- Results
- Posted 27 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the present study is to evaluate the effect of tiotropium + olodaterol fixed dose combination (FDC) compared to tiotropium monotherapy on the intensity of breathlessness during the 3min constant speed shuttle test (CSST).
A secondary objective is to explore the relationship between reductions in breathlessness during the 3min CSST and reductions in breathlessness during activities of everyday living as measured by the dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) following bronchodilator therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tiotropium + Olodaterol | Experimental | Drug: Tiotropium, Drug: OlodaterolPatients will receive tiotropium 5mcg + olodaterol 5mcg in a fixed dose combination once daily. |
| Tiotropium | Active comparator | Drug: Tiotropium |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice guidelines prior to participation in the trial, including medication washout and restrictions
- Diagnosis of Chronic Obstructive Pulmonary Disease and relatively stable airway obstruction: post bronchodilator 30%<= Forced Expiratory Volume in 1st second (FEV1)<80% of predicted normal (European Coal and Steel Community) and a post bronchodilator FEV1/Forced Vital Capacity<0.70 at visit 1
- Male or female patients >=40 and =<75 years of age on day of signing consent.
- Current or ex-smokers with a smoking history > 10 pack-years. Patients who have never smoked cigarettes must be excluded.
- Baseline Dyspnea Index score< 8 at visit 0.
Key exclusion criteria (30 listed)
- Significant disease other than Chronic Obstructive Pulmonary Disease (COPD); a significant disease which, in the investigator's opinion, may (i) put the patient at risk (ii) influence the study results or (iii) cause concern regarding the patient's ability to participate
- Clinically relevant abnormal baseline haematology, blood chemistry, in the investigator's opinion, or creatinine >x2 Upper Limit Normal will be excluded regardless of clinical condition
- Current documented diagnosis of asthma
- COPD exacerbation in the 6 weeks prior to screening
- Diagnosis of thyrotoxicosis
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 |
|---|---|---|
| Tiotropiumfixed dose combination once daily | Drug | Tiotropium + Olodaterol |
| Olodaterolfixed dose combination once daily | Drug | Tiotropium + Olodaterol |
| Tiotropium | Drug | Tiotropium |
Primary outcome
Change From Baseline in Intensity of Breathlessness Measured Using the Modified Borg Scale at the End of the 3 Minute (Min) Constant Speed Shuttle Test After 6 Weeks of Treatment.
Time frame: Baseline and week 6
At 3 min or end of exercise (if 3 min not achieved), patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). The modified Borg scale is 10-point subjective scoring system, in which a patient rates effort of exertion while performing a particular activity. The scale is 0 to 10, the higher the score, the greater the perceived difficulty. Measure type is actually Adjusted Mean Change from Baseline.
7 secondary outcomes
Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured Prior to Exercise
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured at the End of Exercise
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Expiratory Volume
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Vital Capacity
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Intensity of Breathlessness (MBS-S) at 1, 2 and 2.5 Minute (Min) During the 3 Min Constant Speed Shuttle Test
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Individualized (CRQ-SAI) Dyspnoea Domain Score
Time frame: Baseline and week 6
Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) Dyspnoea Domain Score
Time frame: Baseline and week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 13 sites in 4 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 30 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 27 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Canada, Belgium, Germany, Netherlands. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 2019). 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?
Change From Baseline in Intensity of Breathlessness Measured Using the Modified Borg Scale at the End of the 3 Minute (Min) Constant Speed Shuttle Test After 6 Weeks of Treatment. (time frame: Baseline and week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Sep 2019.