Pulmonary Disease, Chronic ObstructiveNCT03405363

Cardiovascular Events in Chronic Obstructive Pulmonary Disease Patients Initiating Olodaterol or Other Long-acting beta2 Agonists

An observational study of Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 1 site in Denmark.

Completed

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

Trial summary

Examine the risk of cardiovascular events (cardiac arrhythmia or myocardial ischemia) or all-cause mortality in Chronic Obstructive Pulmonary Disease (COPD) patients who are new users of Olodaterol or other LABAs available for the treatment of COPD. Read more about this study

Who is it for?: Ages 40 to 100 years
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
How many people: 65,406 participants
Where: 1 siteDenmark
Study dates: 31 Jan 2018to 3 Feb 2020
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 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: COPD patients

Who may be able to join

COPD diagnosis
aged 40 years or older (to minimise the likelihood of including individuals who have asthma only)
New user of olodaterol or a new user of indacaterol, salmeterol, or formoterol (not in fixed-dose combination with an inhaled corticosteroid) and have no dispensing of any LABA in the 6 months before the index date
at least 1 year of enrolment in the electronic database before their first LABA dispensing (defined as the index LABA)
Complete data on sex

Who cannot join

none

Trial locations and contacts

1 site in 1 country.

Denmark1 site

Aarhus Universitets hospital Skejby
Aarhus

Other trials in Denmark

About this study

Official title: Cohort Study of Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease Initiating Olodaterol or Other Long-acting beta2-agonists

Read the detailed description

Purpose:

Time Perspective:

Conditions: Pulmonary Disease, Chronic Obstructive
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.

Study groups in NCT03405363
Study group	Role	What they receive
new users of Olodaterol		COPD patients using Olodaterol for the first time
new users of other LABAs		COPD patients using other long-acting beta2 agonists for the first time

What is being measured

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

Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)
Cases of AF were ascertained by at least one (=first occurrence) International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol.
The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Measured: Up to 4 years and 11 months
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)
Cases of SVT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol.
The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Measured: Up to 4 years and 11 months
Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest
Cases of VT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being exposed to olodaterol and other LABA monotherapy or in free or fixed-dose combination with long-acting muscarinic antagonist (LAMA).
The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Measured: Up to 4 years and 11 months
Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)
Cases of AMI were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol.
The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Measured: Up to 4 years and 11 months
Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events
Cases of SACHD were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol.
The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Measured: Up to 4 years and 11 months.

Secondary outcomes (1)

All-cause Mortality.
Death ascertained from Danish Civil Registration System (fact and date of death, but not cause of death) while being new users of olodaterol or any Long-Acting Beta2-Agonist (LABA) other than olodaterol.
Exposure window: first episode of continuous use (= time comprising consecutive dispensing's separated by up to 14 days). Termination dates of the follow up: date of outcome of interest, disenrollment from database, 14 days after estimated discontinuation of last dispensing for index LABA, date patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
To assess possible impact of imbalanced baseline characteristics, all-cause mortality was further assessed in two post-hoc analyses with restricted populations that would be more similar at baseline, post-hoc population 1 and post-hoc population 2.
Measured: Up to 4 years and 11 months.

Timeline

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

31 Jan 20183 Feb 2020

First posted23 Jan 2018
Study start31 Jan 2018
Primary completion3 Feb 2020
Study completion3 Feb 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: Observational
Observational model: Cohort
Time perspective: Other
Enrolment: 65,406 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03405363
Sponsor's protocol ID: 1222.54
Status last verified: Apr 2021
First submitted: 15 Jan 2018
Last updated: 30 Apr 2021
Results posted: Yes, on ClinicalTrials.gov

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 Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cohort Study of Cardiovascular Events in Patients With Chronic Obstructive Pulmonary Disease Initiating Olodaterol or Other Long-acting beta2-agonists
ClinicalTrials.gov ID: NCT03405363
Acronym / sponsor ID: 1222.54
Conditions: Pulmonary Disease, Chronic Obstructive
Study type: Observational
Recruitment status: Completed
Enrolment: 65,406 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 31 Jan 2018 (actual)
Primary completion: 3 Feb 2020 (actual)
Study completion: 3 Feb 2020 (actual)
First posted: 23 Jan 2018 (actual)
Results: Posted 30 Apr 2021

Clinical summary

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

Detailed description

Purpose:

Time Perspective:

Study design

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

Arm	Type	Receives
new users of Olodaterol	–	–COPD patients using Olodaterol for the first time
new users of other LABAs	–	–COPD patients using other long-acting beta2 agonists for the first time

Who may qualify

Ages: 40 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: COPD patients

Key inclusion criteria (5 listed)

COPD diagnosis
aged 40 years or older (to minimise the likelihood of including individuals who have asthma only)
New user of olodaterol or a new user of indacaterol, salmeterol, or formoterol (not in fixed-dose combination with an inhaled corticosteroid) and have no dispensing of any LABA in the 6 months before the index date
at least 1 year of enrolment in the electronic database before their first LABA dispensing (defined as the index LABA)
Complete data on sex

Key exclusion criteria (1 listed)

none

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)
Time frame: Up to 4 years and 11 months
Cases of AF were ascertained by at least one (=first occurrence) International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)
Time frame: Up to 4 years and 11 months
Cases of SVT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest
Time frame: Up to 4 years and 11 months
Cases of VT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being exposed to olodaterol and other LABA monotherapy or in free or fixed-dose combination with long-acting muscarinic antagonist (LAMA). The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)
Time frame: Up to 4 years and 11 months
Cases of AMI were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events
Time frame: Up to 4 years and 11 months.
Cases of SACHD were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).

1 secondary outcome

All-cause Mortality.
Time frame: Up to 4 years and 11 months.

Results and safety

Results posted to the registry on 30 Apr 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
Olodaterol	14,239	14,239
Other Long-acting beta2-agonist (LABAs)	51,167	51,167

Primary outcome: Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)

Time frame: Up to 4 years and 11 months. Number. Unit: Events

Measure	Olodaterol n = 14239	Other Long-acting beta2-agonist (LABAs) n = 51167
Value	246	725

Olodaterol vs Other Long-acting beta2-agonist (LABAs): Adjusted Incidence Rate Ratio: 1.20 (95% CI 0.98 to 1.47), Poisson regression model

Population analysed: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry

Primary outcome: Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)

Time frame: Up to 4 years and 11 months. Number. Unit: Events

Measure	Olodaterol n = 14239	Other Long-acting beta2-agonist (LABAs) n = 51167
Value	19	38

Olodaterol vs Other Long-acting beta2-agonist (LABAs): Adjusted Incidence Rate Ratio: 1.83 (95% CI 0.90 to 3.74), Poisson regression model

Population analysed: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.

Primary outcome: Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest

Time frame: Up to 4 years and 11 months. Number. Unit: Events

Measure	Olodaterol n = 14239	Other Long-acting beta2-agonist (LABAs) n = 51167
Value	29	80

Olodaterol vs Other Long-acting beta2-agonist (LABAs): Adjusted Incidence Rate Ratio: 1.30 (95% CI 0.71 to 2.36), Poisson regression model

Population analysed: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.

Primary outcome: Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)

Time frame: Up to 4 years and 11 months. Number. Unit: Events

Measure	Olodaterol n = 14239	Other Long-acting beta2-agonist (LABAs) n = 51167
Value	56	137

Olodaterol vs Other Long-acting beta2-agonist (LABAs): Adjusted Incidence Rate Ratio: 1.22 (95% CI 0.79 to 1.87), Poisson regression model

Population analysed: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 4 years and 11 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Olodaterol	0 of 0	0 of 0	859 of 14,239
Other Long-acting beta2-agonist (LABAs)	0 of 0	0 of 0	1,872 of 51,167

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2021.
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

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 Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 1 site in Denmark.

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 1 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 30 Apr 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 Denmark. 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 Apr 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?

Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF) (time frame: Up to 4 years and 11 months). The study lists 5 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 NCT03405363.

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 30 Apr 2021.