COPDNCT04138758

Comparative Effectiveness and Safety of Tiotropium and Olodaterol in Comparison to LABA/ICS

An observational study of COPD, run by Boehringer Ingelheim at 1 site in United States.

Completed

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

Trial summary

The primary objective is to compare the effectiveness of maintenance therapy initiation with the combination treatment Tiotropium and Olodaterol (Olo+Tio) compared with LABA/ICS combination in COPD as the time to the first COPD exacerbation. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: COPD
What is being tested?: Tiotropium bromide + Olodaterol and LABA/ICS
How many people: 42,953 participants
Where: 1 siteUnited States
Study dates: 1 Nov 2019to 4 Nov 2019
Phase: Observational
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

Study population: Subjects with COPD inititated with Tio+Olo in comparison to patients treated with ICS/LABA/LAMA

Who may be able to join

At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019.
The first dispensing of either Tio+Olo or LABA/ICS combined inhaler will be defined as the index date.
For the main analyses, only fixed dose combination (FDC) inhalers will be included. Sensitivity analyses will also accept free combinations of LABA/ICS.
At least one diagnosis of COPD at any time prior to the index date.
At least one year of continuous medical and pharmacy health plan eligibility prior to the index date will be required to allow a baseline period for the covariates and identification of new use of the study drugs.

Who cannot join

To increase the likelihood of a true diagnosis of COPD, we will exclude:
All patients less than 40 years of age on the index date, and
All patients with a diagnosis of asthma in the year prior to the index date
To limit the population to those without severe lung compromise outside of COPD, we will exclude individuals with lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date
To restrict the cohort to new users of Tio+Olo or LABA/ICS, we will exclude any individual with use of either Tio+Olo, LABA/ICS, or LABA/LAMA/ICS combination therapy in free or fixed form for at least one year prior to the index date.

Trial locations and contacts

1 site in 1 country.

United States1 site

HealthCore, Inc.
Watertown, Massachusetts, 02472

Other trials in United States

About this study

Official title: Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids and Long-acting β2 Agonists in COPD Patients

Secondary objectives are to compare patients treated with Tio+Olo and patients treated with LABA/ ICS combination.

Conditions: COPD
Being tested: Tiotropium bromide + Olodaterol, LABA/ICS
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 bromide + OlodaterolDrug
Tiotropium bromide + Olodaterol
LABA/ICSDrug
Long-acting beta2-agonist and Inhaled corticosteroids (LABA and ICS)

Study groups in NCT04138758
Study group	Role	What they receive
Patients initiating Tiotropium+Olodaterol therapy		Not described Receives: Drug: Tiotropium bromide + Olodaterol
Patients initiating Long-acting beta agonist/inhaled corticosteroid therapy		Not described Receives: Drug: LABA/ICS

What is being measured

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

Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows:
Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD.
or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.
Measured: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.

Secondary outcomes (5)

Incidence Rate of First Hospitalization for Community-acquired Pneumonia
Incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes.
Measured: From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy
Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy, (i.e., addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy).
Measured: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy
Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy.
Based on feedback from clinical experts during review of study results, an alternative post-hoc definition was also assessed in which initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination was counted as an outcome.
Measured: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy
Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (original case definition) to triple therapy.
Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.
Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy.
Measured: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy
Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (alternative case definition) to triple therapy.
Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.
Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination.
Measured: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.

Timeline

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

1 Nov 20194 Nov 2019

First posted24 Oct 2019
Study start1 Nov 2019
Primary completion4 Nov 2019
Study completion4 Nov 2019

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 (1)Papers the sponsor has linked to this study.
Other trials for COPDStudies 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: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 42,953 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04138758
Sponsor's protocol ID: 1237-0093
Status last verified: Nov 2021
First submitted: 23 Oct 2019
Last updated: 15 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Publications

Quint JK, Montonen J, Esposito DB, He X, Koerner L, Wallace L, de la Hoz A, Miravitlles M. Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database. Adv Ther. 2021 May;38(5):2249-2270. doi: 10.1007/s12325-021-01646-5. Epub 2021 Mar 15.
PubMed 33721209

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

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All COPD trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids and Long-acting β2 Agonists in COPD Patients
ClinicalTrials.gov ID: NCT04138758
Acronym / sponsor ID: 1237-0093
Conditions: COPD
Study type: Observational
Recruitment status: Completed
Enrolment: 42,953 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 1 Nov 2019 (actual)
Primary completion: 4 Nov 2019 (actual)
Study completion: 4 Nov 2019 (actual)
First posted: 24 Oct 2019 (actual)
Results: Posted 30 Nov 2020

Clinical summary

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

Secondary objectives are to compare patients treated with Tio+Olo and patients treated with LABA/ ICS combination.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
Patients initiating Tiotropium+Olodaterol therapy	–	Drug: Tiotropium bromide + Olodaterol
Patients initiating Long-acting beta agonist/inhaled corticosteroid therapy	–	Drug: LABA/ICS

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Subjects with COPD inititated with Tio+Olo in comparison to patients treated with ICS/LABA/LAMA

Key inclusion criteria (5 listed)

At least one prescription for Tio+Olo combined inhaler or a LABA/ICS combined inhaler between 1 January 2013 and 31 March 2019.
At least one diagnosis of COPD at any time prior to the index date.
At least one year of continuous medical and pharmacy health plan eligibility prior to the index date will be required to allow a baseline period for the covariates and identification of new use of the study drugs.

Key exclusion criteria (5 listed)

To increase the likelihood of a true diagnosis of COPD, we will exclude:
To limit the population to those without severe lung compromise outside of COPD, we will exclude individuals with lung cancer, interstitial lung disease, or lung transplant identified at any time prior to the index date
To restrict the cohort to new users of Tio+Olo or LABA/ICS, we will exclude any individual with use of either Tio+Olo, LABA/ICS, or LABA/LAMA/ICS combination therapy in free or fixed form for at least one year prior to the index date.

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 bromide + OlodaterolTiotropium bromide + Olodaterol	Drug	Patients initiating Tiotropium+Olodaterol therapy
LABA/ICSLong-acting beta2-agonist and Inhaled corticosteroids (LABA and ICS)	Drug	Patients initiating Long-acting beta agonist/inhaled corticosteroid therapy

Primary outcome

Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Time frame: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.
Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.

5 secondary outcomes

Incidence Rate of First Hospitalization for Community-acquired Pneumonia
Time frame: From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy
Time frame: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy
Time frame: From cohort entry (index date) until the escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy
Time frame: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.
Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy
Time frame: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.

Results and safety

Results posted to the registry on 30 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tiotropium + Olodaterol	2,600	2,600
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	40,353	40,353

Primary outcome: Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Time frame: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.. Number (95% Confidence Interval). Unit: Events per 1,000 Person-days

Measure	Tiotropium + Olodaterol n = 2600	Long-acting Beta Agonist / Inhaled Corticosteroid Therapy n = 40353
Value	1.63 (1.47 to 1.81)	2.43 (2.37 to 2.49)

Tiotropium + Olodaterol vs Long-acting Beta Agonist / Inhaled Corticosteroid Therapy: Hazard Ratio (HR): 0.76 (95% CI 0.68 to 0.85)

Population analysed: Propensity score weighted populations of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the HealthCore Integrated Research Database (HIRD, January 2013 - March 2019), who initiated fixed dose combination (FDC) inhaler treatment of Tiotropium and Olodaterol or long-acting beta agonist / inhaled corticosteroid therapy.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tiotropium + Olodaterol	0 of 0	0 of 0	0
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33721209Quint JK, Montonen J, Esposito DB, He X, Koerner L, Wallace L, de la Hoz A, Miravitlles M. Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database. Adv Ther. 2021 May;38(5):2249-2270. doi: 10.1007/s12325-021-01646-5. Epub 2021 Mar 15.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

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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.

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of COPD, run by Boehringer Ingelheim at 1 site in United States.

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 5 inclusion and 5 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 15 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 1 site in United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2020). 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?

Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation (time frame: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.). 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 NCT04138758, which also lists 1 linked publication.

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 15 Nov 2021.