Status: Planned
First registered on:
06/04/2017
Last updated on:
06/04/2017
1. Study identification
EU PAS Register NumberEUPAS18510
Official titleAssessment of cardiovascular effects of non-insulin glucose-lowering agents. Major cardiovascular events in new users of non-insulin glucose-lowering agents: observational longitudinal study in the Catalan population-based electronic health record database, SIDIAP, 2010-2015
Study title acronym
Study typeObservational study
Brief description of the studyCardiovascular (CV) risk is the leading cause of morbidity and mortality in T2DM population. The effect of control serum glucose levels on macrovascular complications remains uncertain. Glucose-lowering agents are currently marketed based on results of clinical trials with subrogate variables, mainly the percentage of glycated haemoglobin and other glucose markers. In 2007, concerns about CV safety of rosiglitazone led to regulatory recommendations regarding CV risk of new hypoglycemic agents, which are in force since 2008 (FDA, US) and 2012 (EMA, EU). In order to fulfill these recommendations, since 2008 a number of large randomized clinical trials have been designed and conducted, with a non-inferiority design as basis, with controversial results. Other ten large RCTs, on-going or recently completed, are currently assessing the CV effect of seven marketed agents are currently unavailable.
Aim: To evaluate the effect of currently marketed non-insulin glucose-lowering agents on major CV outcomes in cohorts of Spanish population based on records of population-based EMR SIDIAP.
Design: Longitudinal retrospective observational cohort study, period of observation of six years (1st January 2010- 31st Dec 2015)
Material and Methods: Cohorts of patients aged 18 yrs. or older registered in the SIDIAP database, diagnosed of type 2 diabetes mellitus, and treated with approved glucose-lowering agents since their first prescription. Patients will be stratified by demographic and clinical variables. The incidence rate of the first major cardiovascular event will be calculated. The primary outcome (PCO) is the composite of CV death, non-fatal myocardium infarction (MI) and non-fatal stroke. Secondary outcomes are: composite (SCO) of CV death, a non-fatal myocardium infarction (MI), non-fatal stroke and hospitalization due to unstable angina or coronary revascularization procedures; individual components of SCO, hospitalization due to HF (HHF) and all-cause mortality.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsFICF
Department/Research group
Organisation/affiliationFundació Institut Català de Farmacologia
Details of (Primary) lead investigator
Title Dr
Last name Vidal
First name Xavier
Is this study being carried out with the collaboration of a research network?
No
Other centres where this study is being conducted
Not applicable (single centre)
Countries in which this study is being conducted
National study
Spain
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed01/07/2016
Start date of data collection01/09/2016
Start date of data analysis01/03/2017
Date of interim report, if expected
Date of final study report01/03/2018
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
CharitiesIDIAP Jordi Gol100
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Vidal
First name Xavier
Address line 1Vall d'Hebron 119-129
Address line 2Antiga Escola Infermeria
Address line 3Servei de Farmacologia Clínica
CityBarcelona
Postcode08035
CountrySpain
Phone number (incl. country code)34934894106
Alternative phone number
Fax number (incl. country code)
Public Enquiries
Title Dr
Last name Vidal
First name Xavier
Address line 1Vall d'Hebron 119-129
Address line 2Antiga Escola Infermeria
Address line 3Servei de Farmacologia Clínica
CityBarcelona
Postcode08035
CountrySpain
Phone number (incl. country code)34934894106
Alternative phone number
Fax number (incl. country code)
6. Study drug(s) information
Substance class (ATC Code)A10B (BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS)
7. Medical conditions to be studied
Medical condition(s)No
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
9. Number of subjects
Estimated total number of subjects270000
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Sources of data
Routine primary care electronic patient registry
Pharmacy dispensing records
11. Scope of the study
What is the scope of the study?
Effectiveness evaluation
Primary scope : Effectiveness evaluation
12. Main objective(s)
What is the main objective of the study?
To evaluate the effect of currently marketed non-insulin glucose-lowering agents on major CV outcomes in cohorts of Spanish population based on records of population-based EMR SIDIAP
Are there primary outcomes?Yes
Composite of three-components of mayor cardiovascular events (MACE): cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke.
Are there secondary outcomes?Yes
Secondary Composite Outcome is a MACE of four components: CV death, non-fatal MI, non-fatal stroke and hospitalization due to unstable angina or coronary revascularization procedures
13. Study design
What is the design of the study?
Cohort study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Patients were followed up until the outcomes’ occurrence, lost to follow-up or end of observation. Patients were also censored when they initiated a new non-insulin glucose-lowering treatment, because this is the entry in another cohort
15. Data analysis plan
Please provide a brief summary of the analysis method
Incidence rates of primary and secondary composite outcomes events and secondary outcomes events will be estimated for each cohort during follow-up. Incident rates will be presented per 1000 patient-years and their corresponding 95% confidence intervals (CIs).
Hazard ratios of PCO, SCO and SO will be calculated between cohorts (treated vs. non-treated) for each therapeutic group and, secondarily, for each given agent. Data will be analysed with multivariate Cox proportional-hazard regression models, once verified proporcionality assumptions.
To control potential biases for confounding factors, the differences between exposed and non-exposed populations to the different hypoglycemic agents will be adjusted by estimating a propensity index using a logistic regression model. In order to control the effect of time-dependent confounders the use of marginal structural models will be also considered.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
Available when the study ends
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documentsNot
submitted
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
