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

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive

• Registration Number: NCT02096731
• Lead Sponsor: Boehringer Ingelheim

Brief 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. Finally, pneumonia was the object of a recent signal in trials of LABAs submitted for marketing approval.

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.

Detailed Description

Purpose:

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-24
• Study First Submitted QC: 2014-03-24
• Study First Posted: 2014-03-26
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Results First Submitted: 2016-07-28
• Status Verified: 2016-12
• Results First Submitted QC: 2016-12-22
• Last Update Submitted: 2016-12-22
• Results First Posted: 2017-02-15
• Last Update Posted: 2017-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 115397

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cardiac Arrhythmia	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	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
Myocardial Infarction	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	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	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.

Trial Locations

Locations (1)

Boehringer Ingelheim Investigational Site; 🇨🇦 Montreal, Quebec, Canada