Pulmonary Disease, Chronic ObstructiveNCT02096731

Combined Bronchodilators in Chronic Obstructive Pulmonary Disease and the Risk of Adverse Cardio-pulmonary Events

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

Completed

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

Trial summary

Background: Recent observational studies have reported possible arrhythmogenic effects with long-acting beta-agonists (LABA), while the long-acting anticholinergic tiotropium has been associated with cardiovascular and cerebrovascular events. Read more about this study

Who is it for?: Ages 55 to 100 years
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
How many people: 115,397 participants
Where: 1 siteCanada
Study dates: Mar 2014to Aug 2015
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 55 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: Users of tiotropium or long-acting beta agonists

Who may be able to join

New users of long-acting bronchodilators, either a LABA or tiotropium, between January 2002 and August 2012
Age >= 55 years

Who cannot join

Use of LABA or tiotropium in the two years prior to cohort entry

Trial locations and contacts

1 site in 1 country.

Canada1 site

Boehringer Ingelheim Investigational Site
Montreal, Quebec

Other trials in Canada

About this study

Official title: Combined Bronchodilators in Chronic Obstructive Pulmonary Disease and the Risk of Adverse Cardio-pulmonary Events: A Population-based Observational Study

Aim: To assess the potential cardio-pulmonary risk arising from the concurrent use of two long-acting bronchodilators as well as from monotherapy use of each of the long-acting bronchodilators.

Methods: A series of population-based cohort studies, using both cohort and nested case-control analyses will be conducted using data from the United Kingdom's Clinical Practice Research Datalink (CPRD). The base cohort will consist of new users of long-acting bronchodilators from Jan 2002 until Aug 2012, age >= 55 with chronic obstructive pulmonary disease (COPD) and at least two years of baseline medical history information. The high-dimensional propensity score technique will be used to match new users of each long-acting bronchodilator and new users of two bronchodilators with comparable subjects from the base cohort, with one-year follow-up for outcomes of acute myocardial infarction, stroke, heart failure, arrhythmia and community acquired pneumonia. Data will be analysed using time-dependent Cox proportional hazard regression models and conditional logistic regression models.

Read the detailed description

Purpose:

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 NCT02096731
Study group	Role	What they receive
LABA + tiotropium		Not described
LABA mono		Not described
neither tiotropium nor LABA		Not described
tiotropium + LABA		Not described
tiotropium mono		Not described

What is being measured

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

Myocardial Infarction
The acute myocardial infarction (MI) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
No. = Number
Measured: Up to 12 months
Stroke
The stroke rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Measured: Up to 12 months
Heart Failure
The heart failure (HF) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Measured: Up to 12 months
Cardiac Arrhythmia
The cardiac arrhythmia (CA) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Measured: Up to 12 months
Community Acquired Pneumonia
The community acquired pneumonia rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Pt. = Patient
Measured: Up to 12 months

Timeline

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

Mar 2014Aug 2015

First posted26 Mar 2014 (estimated)
Study startMar 2014
Primary completionAug 2015
Study completionAug 2015

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: Retrospective
Enrolment: 115,397 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02096731
Sponsor's protocol ID: 205.526
Status last verified: Dec 2016
First submitted: 24 Mar 2014
Last updated: 15 Feb 2017
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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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
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All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Combined Bronchodilators in Chronic Obstructive Pulmonary Disease and the Risk of Adverse Cardio-pulmonary Events: A Population-based Observational Study
ClinicalTrials.gov ID: NCT02096731
Acronym / sponsor ID: 205.526
Conditions: Pulmonary Disease, Chronic Obstructive
Study type: Observational
Recruitment status: Completed
Enrolment: 115,397 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Mar 2014
Primary completion: Aug 2015 (actual)
Study completion: Aug 2015 (actual)
First posted: 26 Mar 2014 (estimated)
Results: Posted 15 Feb 2017

Clinical summary

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

Aim: To assess the potential cardio-pulmonary risk arising from the concurrent use of two long-acting bronchodilators as well as from monotherapy use of each of the long-acting bronchodilators.

Detailed description

Purpose:

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 5

Arm	Type	Receives
LABA + tiotropium	–	–
LABA mono	–	–
neither tiotropium nor LABA	–	–
tiotropium + LABA	–	–
tiotropium mono	–	–

Who may qualify

Ages: 55 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Users of tiotropium or long-acting beta agonists

Key inclusion criteria (2 listed)

New users of long-acting bronchodilators, either a LABA or tiotropium, between January 2002 and August 2012
Age >= 55 years

Key exclusion criteria (1 listed)

Use of LABA or tiotropium in the two years prior to cohort entry

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

Myocardial Infarction
Time frame: Up to 12 months
The acute myocardial infarction (MI) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. No. = Number
Stroke
Time frame: Up to 12 months
The stroke rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Heart Failure
Time frame: Up to 12 months
The heart failure (HF) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Cardiac Arrhythmia
Time frame: Up to 12 months
The cardiac arrhythmia (CA) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry.
Community Acquired Pneumonia
Time frame: Up to 12 months
The community acquired pneumonia rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. Pt. = Patient

Results and safety

Results posted to the registry on 15 Feb 2017, 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	26,442	26,442
LABA	88,955	88,955

Primary outcome: Myocardial Infarction

Time frame: Up to 12 months. Number. Unit: No. of incident MI/1000patients/ year

Measure	Monotherapy n = 31138	Combination Therapy n = 31138
Value	10.1	11.3

Monotherapy vs Combination Therapy: Hazard Ratio (HR): 1.12 (95% CI 0.92 to 1.37)

Population analysed: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium) and were matched via propensity score.

Primary outcome: Stroke

Time frame: Up to 12 months. Number. Unit: No. of incident stroke/1000patients/year

Measure	Monotherapy n = 31123	Combination Therapy n = 31123
Value	8.3	7.0

Monotherapy vs Combination Therapy: Hazard Ratio (HR): 0.87 (95% CI 0.69 to 1.10)

Primary outcome: Heart Failure

Time frame: Up to 12 months. Number. Unit: No. of incident HF/1000patients/year

Measure	Monotherapy n = 31174	Combination Therapy n = 31174
Value	29.3	33.9

Monotherapy vs Combination Therapy: Hazard Ratio (HR): 1.16 (95% CI 1.03 to 1.30)

Primary outcome: Cardiac Arrhythmia

Time frame: Up to 12 months. Number. Unit: No. of incident CA/1000patients /year

Measure	Monotherapy n = 18861	Combination Therapy n = 18861
Value	10.0	10.7

Monotherapy vs Combination Therapy: Hazard Ratio (HR): 1.05 (95% CI 0.81 to 1.36)

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tiotropium	0 of 0	0 of 0	Not reported
LABA	0 of 0	0 of 0	Not reported

Limitations and caveats (from the sponsor): Study measures may be subject to misclassification. Diagnoses codes based on read codes and not laboratory or clinical measures. Residual confounding is possible as the analysis is dependent on only recorded information in patients' clinical records.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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
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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
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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 Canada.

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 2 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 15 Feb 2017. 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 Canada. 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 15 Feb 2017). 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?

Myocardial Infarction (time frame: Up to 12 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 NCT02096731.

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 Feb 2017.