Pulmonary Disease, Chronic ObstructivePhase 4NCT04223843

A Study to Test the Combination of Tiotropium and Olodaterol Using the Respimat® Inhaler in People With Chronic Obstructive Pulmonary Disease (COPD) Who Have Different Abilities to Inhale

A Phase 4 study testing Tiotropium + olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To demonstrate the efficacy of inhaled tiotropium + olodaterol via Respimat® on lung function in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) with optimal and sub-optimal Peak Inspiratory Flow Rate (PIFR). Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Tiotropium + olodaterol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 213 participants
Where: 26 sitesin 2 countries
Study dates: 8 Jan 2020to 29 Sep 2020
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed and dated written informed consent in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
Male or female patients, 40 years of age or older.
All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) >30% and <80% of predicted normal (European Coal and Steel Community (ECSC), [R94-1408]); and a postbronchodilator FEV1/ Functional Residual Capacity (FVC) <70%, at the screening visit.
Patients must be current or ex-smokers with a smoking history of more than 10 pack years
Patients should meet the peak inspiratory flow rate criteria (optimal or sub-optimal) at the time of randomization depending on which strata is available for inclusion in the study.
Women of childbearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

Show all 11Show fewer

Patients are expected to be able to perform, according to investigator's judgment, all trial related procedures including:
Technically acceptable pulmonary function tests (spirometry)
Use of In-Check DIAL G16 device to measure peak inspiratory flow rate.
Inhale medication in a competent manner (in the opinion of the investigator) from the Respimat® device
Perform technically acceptable body plethysmography measurements. This is applicable only to patients who will consent to the optional trial procedure at the selected sites.

Who cannot join

Patients with a significant disease other than chronic obstructive pulmonary disease; a significant disease defined as a disease which, in the opinion of the investigator, and referring to the warnings to be observed as quoted in the locally applicable SmPC or prescribing information, could (i) put the patient at risk because of participation in the trial, (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
Patients who have had a chronic obstructive pulmonary disease exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to screening visit or during the screening period.
Patients who experienced two or more moderate chronic obstructive pulmonary disease exacerbations (exacerbation that required treatment with antibiotics and/or oral corticosteroids), or one or more exacerbation leading to hospitalization within a year prior to visit 1.
Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
Patients taking inhaled corticosteroids (including combinations, e.g. inhaled corticosteroids / Long-Acting β2-agonist) in the 6 months prior to screening visit.
Patients being treated with oral corticosteroid medication due to reasons other than chronic obstructive pulmonary disease exacerbation within 6 weeks prior to the screening visit.
Patients who have completed a pulmonary rehabilitation program in the 6 weeks prior to screening visit or patients who are currently in a pulmonary rehabilitation program.
Further criteria apply

Trial locations and contacts

26 sites in 2 countries.

Country

City, postcode or hospital

26 sites in 2 countries

United States21 sites

SEC Lung
Andalusia, Alabama, 36420
Meris Clinical Research
Brandon, Florida, 33511
Lowcountry Lung and Critical Care
Charleston, South Carolina, 29406
Bernstein Clinical Rsrch Ctr
Cincinnati, Ohio, 45231
Valley Regional Hospital
Claremont, New Hampshire, 03743
Clinical Research of West Florida, Inc.
Clearwater, Florida, 33765
Carolina Medical Research
Clinton, South Carolina, 29325
Minnesota Lung Center and Sleep Institute
Edina, Minnesota, 55435
Pulmonary Rsrch Inst of SE MI
Farmington Hills, Michigan, 48152
VitaLink Research -Gaffney
Gaffney, South Carolina, 29340
Jasper Summit Research, LLC
Jasper, Alabama, 35501
Clinical Research Specialists LLC
Kissimmee, Florida, 34746
Best Clinical Trials, LLC
New Orleans, Louisiana, 70115
Infinity Medical Research
North Dartmouth, Massachusetts, 02747
North Carolina Clinical Research
Raleigh, North Carolina, 27607
Diagnostics Research Group
San Antonio, Texas, 78229
Vitalink Research - Spartansburg
Spartanburg, South Carolina, 29303
Clinical Research of West Florida, Inc.
Tampa, Florida, 33606
CHEAR Center LLC
The Bronx, New York, 10455
Southeastern Research Center
Winston-Salem, North Carolina, 27103
Minnesota Lung Center
Woodbury, Minnesota, 55125

Other trials in United States

Germany5 sites

Klinische Forschung Berlin GbR
Berlin, 10787
IKF Pneumologie GmbH & Co. KG
Frankfurt, 60596
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927
Hamburger Institut für Therapieforschung GmbH (HIT)
Hamburg, 20354
KLB Gesundheitsforschung Lübeck GmbH
Lübeck, 23552

Other trials in Germany

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Compare the Efficacy of Inhaled Tiotropium + Olodaterol, Fixed Dose Combination (5 mcg/5mcg) vs. Placebo Delivered by Respimat Inhaler in Patients With Moderate to Severe COPD, Stratified by Peak Inspiratory Flow Rate [TRONARTO].

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: Tiotropium + olodaterol, Placebo
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.

Tiotropium + olodaterolDrug
Oral Inhalation
PlaceboDrug
Oral Inhalation

Study groups in NCT04223843
Study group	Role	What they receive
Active Arm	Experimental	Tiotropium + Olodaterol Fixed Dose Combination (FDC) via Respimat Receives: Drug: Tiotropium + olodaterol
Placebo Arm	Placebo comparator	Matching placebo via Respimat Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.
FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean.
A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful.
Measured: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.

Secondary outcomes (1)

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment
Change from baseline in trough Forced Expiratory Volume in one second (FEV1) after 4 weeks of treatment.
Measured: At baseline and at week 4.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Jan 202029 Sep 2020

First posted10 Jan 2020
Study start8 Jan 2020
Primary completion7 Sep 2020
Study completion29 Sep 2020

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: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 213 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04223843
Sponsor's protocol ID: 1237-0095
Other IDs: 2019-001719-21, 2019
Status last verified: Oct 2021
First submitted: 7 Jan 2020
Last updated: 18 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease

All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Compare the Efficacy of Inhaled Tiotropium + Olodaterol, Fixed Dose Combination (5 mcg/5mcg) vs. Placebo Delivered by Respimat Inhaler in Patients With Moderate to Severe COPD, Stratified by Peak Inspiratory Flow Rate [TRONARTO].
ClinicalTrials.gov ID: NCT04223843
Acronym / sponsor ID: 1237-0095
Conditions: Pulmonary Disease, Chronic Obstructive
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 213 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 8 Jan 2020 (actual)
Primary completion: 7 Sep 2020 (actual)
Study completion: 29 Sep 2020 (actual)
First posted: 10 Jan 2020 (actual)
Results: Posted 18 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Active Arm	Experimental	Drug: Tiotropium + olodaterolTiotropium + Olodaterol Fixed Dose Combination (FDC) via Respimat
Placebo Arm	Placebo comparator	Drug: PlaceboMatching placebo via Respimat

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Signed and dated written informed consent in accordance with International Council on Harmonisation Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
Male or female patients, 40 years of age or older.
All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) >30% and <80% of predicted normal (European Coal and Steel Community (ECSC), [R94-1408]); and a postbronchodilator FEV1/ Functional Residual Capacity (FVC) <70%, at the screening visit.
Patients must be current or ex-smokers with a smoking history of more than 10 pack years
Patients should meet the peak inspiratory flow rate criteria (optimal or sub-optimal) at the time of randomization depending on which strata is available for inclusion in the study.

Key exclusion criteria (8 listed)

Patients with a significant disease other than chronic obstructive pulmonary disease; a significant disease defined as a disease which, in the opinion of the investigator, and referring to the warnings to be observed as quoted in the locally applicable SmPC or prescribing information, could (i) put the patient at risk because of participation in the trial, (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
Patients who have had a chronic obstructive pulmonary disease exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to screening visit or during the screening period.
Patients who experienced two or more moderate chronic obstructive pulmonary disease exacerbations (exacerbation that required treatment with antibiotics and/or oral corticosteroids), or one or more exacerbation leading to hospitalization within a year prior to visit 1.
Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
Patients taking inhaled corticosteroids (including combinations, e.g. inhaled corticosteroids / Long-Acting β2-agonist) in the 6 months prior to screening visit.

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 + olodaterolOral Inhalation	Drug	Active Arm
PlaceboOral Inhalation	Drug	Placebo Arm

Primary outcome

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.
Time frame: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.
FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean. A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful.

1 secondary outcome

Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment
Time frame: At baseline and at week 4.

Results and safety

Results posted to the registry on 18 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tio+Olo (5μg/5μg) - Sub-optimal PIFR	55	55
Matching Placebo - Sub-optimal PIFR	55	55
Tio+Olo (5μg/5μg ) - Optimal PIFR	51	51
Matching Placebo - Optimal PIFR	52	52

Primary outcome: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.

Time frame: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.. Mean (Standard Error). Unit: Liter (L)

Measure	Tio+Olo (5μg/5μg) - Sub-optimal PIFR n = 43	Matching Placebo - Sub-optimal PIFR n = 47	Tio+Olo (5μg/5μg ) - Optimal PIFR n = 44	Matching Placebo - Optimal PIFR n = 47
Value	0.250 (0.033)	-0.086 (0.031)	0.333 (0.032)	0.012 (0.031)

Tio+Olo (5μg/5μg) - Sub-optimal PIFR vs Matching Placebo - Sub-optimal PIFR: Difference of adjusted means: 0.336 (95% CI 0.246 to 0.425), p <0.0001, ANCOVA
Tio+Olo (5μg/5μg ) - Optimal PIFR vs Matching Placebo - Optimal PIFR: Difference of adjusted means: 0.321 (95% CI 0.233 to 0.409), p <0.0001, ANCOVA

Population analysed: Full Analysis Set (FAS): This patient set was nested within the TS and included all patients who had a baseline and at least 1 post-baseline measurement for at least 1 efficacy endpoint. Only patients with non-missing endpoint results were included.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From first intake of trial medication until last trial medication intake plus 21 days (residual effect period), up to 50 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
5μg/5μg Tio+Olo - Overall	2 of 106 (1.9%)	0 of 106 (0%)	0 of 106
Matching Placebo - Overall	1 of 107 (0.9%)	0 of 107 (0%)	0 of 107

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.

Related trials for Pulmonary Disease, Chronic Obstructive

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease

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.

The record lists no contact. Use the official record to reach the sponsor.

26 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tiotropium + olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 26 sites in 2 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 11 inclusion and 8 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 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Germany. 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. Some participants in this study may receive a placebo. 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 18 Nov 2021). 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 Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment. (time frame: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.). 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 NCT04223843.

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 18 Nov 2021; AzTrials last refreshed its copy on 7 Nov 2026.