CClinicalTrials.gg
CompletedNCT03405363Updated Apr 30, 2021Results posted

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

An observational study in Pulmonary Disease, Chronic Obstructive, sponsored by Boehringer Ingelheim. Completed at 1 site in Denmark. Open to participants aged 40 Years to 100 Years. Per ClinicalTrials.gov, last updated 2021-04-30.

Sponsored by Boehringer Ingelheim · Observational

Study type
Observational
Model
Cohort
Time perspective
Other
Enrollment
65,406
Ages
40 Years to 100 Years
Sex
All
01

Study 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 the detailed description

Purpose:

Time Perspective:

02

Conditions studied

03

Who can participate

Ages eligible
40 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Probability sample

Study population

COPD patients

Inclusion criteria

  • 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

Exclusion criteria

Exclusion criteria:

none

04

Study design

Observational model
Cohort
Time perspective
Other
Enrollment
65,406 participants (actual)
Patient registry
No

Groups and cohorts

  • 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

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Up to 4 years and 11 months

  2. 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).

    Time frame: Up to 4 years and 11 months

  3. 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).

    Time frame: Up to 4 years and 11 months

  4. 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).

    Time frame: Up to 4 years and 11 months

  5. 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).

    Time frame: 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.

    Time frame: Up to 4 years and 11 months.

06

Results

Posted Apr 30, 2021

Participant flow

This cohort study, used data from the Danish National Patient Registry (diagnoses), Danish Prescription Database (dispensings), and Danish Register of Causes of Death (cause of death information) to examine the risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) exposed to olodaterol compared to other long-acting beta2-agonists (LABAs) between 01 March 2014 and 31 January 2019.

Participant flow — Overall Study
MilestoneOlodaterolOther Long-acting beta2-agonist (LABAs)
Started1423951167
Completed1423951167
Not completed00

Outcome measures

PrimaryOccurrence 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).

Time frame:
Up to 4 years and 11 months
Reported as:
Number · Events
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)246725
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.20 · 95% CI 0.98 to 1.47Olodaterol compared to 'other LABA' as reference
PrimaryOccurrence 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).

Time frame:
Up to 4 years and 11 months
Reported as:
Number · Events
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)1938
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.83 · 95% CI 0.90 to 3.74Olodaterol compared to 'other LABA' as reference
PrimaryOccurrence 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).

Time frame:
Up to 4 years and 11 months
Reported as:
Number · Events
Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest2980
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.30 · 95% CI 0.71 to 2.36Olodaterol compared to 'other LABA' as reference
PrimaryOccurrence 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).

Time frame:
Up to 4 years and 11 months
Reported as:
Number · Events
Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)56137
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.22 · 95% CI 0.79 to 1.87Olodaterol compared to 'other LABA' as reference
PrimaryOccurrence 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).

Time frame:
Up to 4 years and 11 months.
Reported as:
Number · Events
Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events41147
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.00 · 95% CI 0.64 to 1.56Olodaterol compared to 'other LABA' as reference
SecondaryAll-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.

Time frame:
Up to 4 years and 11 months.
Reported as:
Number · Events
All-cause Mortality.
EventsOlodaterolOther Long-acting beta2-agonist (LABAs)
All-cause Mortality.8591872
Statistical analysis
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.63 · 95% CI 1.44 to 1.84Olodaterol compared to 'other LABA' as reference
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidence rate ratio: 1.48 · 95% CI 1.23 to 1.78Olodaterol compared to 'other LABA' as reference
  • Olodaterol vs Other Long-acting beta2-agonist (LABAs) · Poisson regression model · Adjusted incidende rate ratio: 1.26 · 95% CI 0.97 to 1.64Olodaterol compared to 'other LABA' as reference

Adverse events

Collected over Up to 4 years and 11 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Olodaterol859/14,239 (6%)——
Other Long-acting beta2-agonist (LABAs)1,872/51,167 (3.7%)——

Baseline characteristics

Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry initiating olodaterol (either alone or in free- or fixed-dose combination with a LAMA) or an alternative LABA (alone or in a free- or fixed-dose combination with a LAMA).

Age, Continuous
Age, Continuous(Years)OlodaterolOther Long-acting beta2-agonist (LABAs)Total
Mean72.7 ± 10.072.7 ± 10.072.7 ± 10.0
Sex: Female, Male
Sex: Female, Male(Participants)OlodaterolOther Long-acting beta2-agonist (LABAs)Total
Female76492725334902
Male65902391430504
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)OlodaterolOther Long-acting beta2-agonist (LABAs)Total
Count of participants——0
07

Study locations

1 site
  • Aarhus Universitets hospital Skejby
    Aarhus, Denmark
08

References and documents

Related links

Study documents

  • Protocol and statistical analysis plan · Oct 28, 2016

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03405363
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Jan 23, 2018
Start date
Jan 31, 2018
Primary completion
Feb 3, 2020
Completion
Feb 3, 2020
Results posted
Apr 30, 2021
Last update
Apr 30, 2021

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim
View the source record on ClinicalTrials.gov ↗

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