- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01636726
WEUKBRE5554: IMI PROTECT(Work Package 2): Beta2 Agonists and Acute Myocardial Infarction
WEUKBRE5554: IMI PROTECT (Work Package 2): Use of Long Acting beta2 Adrenoceptor Agonists and Acute Myocardial Infarction (AMI)
The studies described in this protocol are all performed within the framework of PROTECT (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium) Work Package 2 and Workgroup 1. Primary aim of these studies is to develop, test and disseminate methodological standards for the design, conduct and analysis of Pharmacoepidemiological (PE) studies applicable to different safety issues and using different data sources. To achieve this, results from PE studies on five key adverse events (AEs) performed in different databases will be evaluated. Therefore, emphasis will be on the methodological aspects of the studies in this protocol and not on the clinical consequences of the association under investigation .
Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic airway diseases in the western world. For both, a stepwise treatment to reduce symptoms, improve lung function, and prevent risk of exacerbation is recommended using several drug classes according to guidelines published by e.g. the Global Initiative for Asthma [GINA guideline] and the Global Initiative for Chronic Obstructive Lung Disease [GOLD guideline], respectively. Beta-2-adrenoceptor agonists (B2A) are therapeutic mainstays in treating asthma and COPD due to their bronchodilative effects mediated by B2A. This drug class consists of two types of drugs: short acting B2A (SABA) which are used as a reliever medication and long acting B2A (LABA) which are used as maintenance / controller medication. Formoterol and salmeterol are the most frequently used LABA compounds with a half-life between 5-15 hrs and therefore, these compounds most commonly have labelled indications for use twice a day. .
Focussing on cardiac side effects of B2A one must consider that drugs with an opposite mechanism of action (beta-adrenoceptor-antagonists) have well-known cardio protective effects and are widely used in patients suffering from e.g. ischemic heart disease, hypertension and acute myocardial infarction (AMI)). Conversely, stimulation of cardiac beta-adrenoceptors as done by B2A may have deleterious cardiovascular effects particularly in patients with cardiac risk factors. And in fact, tachycardia and arrhythmias are well-known side effects of B2A confirming a cardiac influence of these drugs particularly after oral therapy (due to a high systemic exposure) as stated in the respective summary of product characteristics (SPCs), e.g. clenbuterol (Spiropent(R)). Obviously, inhaled drugs cause much smaller systemic exposure but cardiac side effects (e.g. arrhythmias, tachycardia) are also described in the respective SPCs (e.g. formoterol [Foradil(R)). Furthermore, cardiac side were also reported after exposure with inhaled MA (e.g. ipratropium [Atrovent(R)].
Several observational studies have been performed on the association between the usage of inhaled B2A and the occurrence of AMI. However, these studies have produced conflicting results. Reasons for this variation are numerous, e.g. small number of events (AMI) leading to poor precision of risk estimate, potential misclassification of potential cardiac events versus airway-related events due to similar clinical complaints, differences in populations of drug users, measurement of drug exposure, and background risk of AMI. Additionally, a consensus document was released in 2000, redefining AMI.
To make comparing results possible, this protocol gives guidelines for conducting studies in the same way in five databases and across 3 designs (cohort, nested case-control, case-cross-over) on the association between inhaled LABA use and AMI. The main focus is to evaluate the impact of study design, population and database characteristics on the association between inhaled LABA and AMI.
Data will be collected from the following databases: The Health Improvement Network (THIN), the General Practice Research Database (GPRD), the Dutch Mondriaan project, Base de Datos para la Investigación Farmacoepidemiológica en Atencion Primaria (BIFAP), the National Databases of Denmark, and the Bavarian statutory health insurance physicians' association database.
Study Overview
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Descriptive study - all patients included in the period of valid data collection. The study period will be defined from Jan 1, 2002 to Dec 31, 2009.
Cohort and nested case-control studies - all patients who received at least one prescription of an inhaled LABA, SABA, LAMA, or SAMA and with coded diagnosis of asthma and / or COPD during the study period.
Description
Inclusion Criteria:
For the descriptive sudy:
- patients who have at least one documented and valid data record in the period from Jan 1, 2002 to Dec 31, 2009
- patients who have a diagnosis of asthma and/or COPD
For the cohort and nested case-control studies:
- patients who have at least one documented and valid data record in the period from Jan 1, 2002 to Dec 31, 2009
- patients who have a diagnosis of asthma and/or COPD
- patients who have at least one prescription of LABA/LAMA/SABA/SAMA
Exclusion criteria:
For the cohort and nested case-control studies:
- patients who had AMI within 1 year before the index date
Study Plan
How is the study designed?
Design Details
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Patients with AMI
All patients of the study population with a record/diagnosis of AMI during the study period
|
LABA prescription during the study period between Jan 1, 2002 and Dec 31, 2009
|
Patients without AMI
All patients of the study population without a record/diagnosis of AMI during the study period
|
LABA prescription during the study period between Jan 1, 2002 and Dec 31, 2009
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The first Acute Myocardial Infarction (AMI) in the study period
Time Frame: Up to eight years following drug exposure
|
Up to eight years following drug exposure
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 115733
- WEUKBRE5554 (Other Identifier: GSK)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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