The CVD-REAL study

View Countries
Current status: Number of countries 12 Patients involved ~4,000,000

  • North America
    • USA
    • Canada
  • Europe
    • Denmark
    • Germany
    • Norway
    • Sweden
    • UK
  • ASIA-PACIFIC
    • South Korea
    • Japan
    • Singapore
    • Australia
  • MIDDLE EAST
    • Israel

Country

  • Number of patients involved: xx
  • Databases involved: xx
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USA,~840 000,Truven Health-MarketScan
Denmark,~130 000,National full-population registries linked to Prescribed Drug Registers National Patient Registers and Cause of Death Registers.
Germany,~26 000,Diabetes Patientenverlaufsdokumentation (DPV) register
Norway,~111 000,National full-population registries linked to Prescribed Drug Registers National Patient Registers and Cause of Death Registers.
Sweden,~210 000,National full-population registries linked to Prescribed Drug Registers National Patient Registers and Cause of Death Registers.
UK,~81 000,The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD)
South Korea,~2 000 000,National Health Insurance Service (NHI) and Health Insurance Review Agency (HIRA)
Japan,~250 000,Medical Data Vision (MDV)
Singapore,~30 000,SingHealth
Australia,~200 000,National Diabetes Service Scheme (NDSS)
Canada,~50 000,MCHP Population Health Research Data Repository
Israel,~50 000,Maccabi Healthcare Services (MHS)
Study map infographic from homepage

CVD-REAL enrollment status last updated February 2017.

CVD-REAL enrollment last updated March 2018

Rationale

Type 2 diabetes mellitus remains a major risk factor for cardiovascular disease with an estimated 425 million adults worldwide having diabetes in 2017, with type 2 diabetes mellitus accounting for about 90% of cases2. Recent evidence indicates that certain glucose-lowering therapies are associated with positive cardiovascular effects. There is, therefore, an urgent need to improve understanding of the impact of newer classes of glucose-lowering therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in clinical practice.

Aim

CVD-REAL is a comparative effectiveness study that aims to compare new users of SGLT-2 inhibitors with new users of other glucose-lowering drugs with regard to the risk of clinically relevant CV outcomes (including stroke, myocardial infarction, and hospitalization for heart failure) as well as all-cause mortality. The study analysis is based on data from 12 countries across four major world regions.

Design

CVD-REAL is a multinational, observational cohort study. The study is conducted using data from claims, medical records and national health registries from twelve countries combined in two waves. CVD-REAL 1 includes Germany, Denmark, Norway, Sweden, United Kingdom (UK) and United States of America (USA). CVD-REAL 2 comprises Australia, Canada, Israel, Japan, Singapore and South Korea as illustrated in the interactive map above. The study will collect data from approximately 4 million patients from the time they start treatment with an SGLT-2 inhibitor or another glucose-lowering drug (index date) to the end of the follow-up period.

CVD-REAL study timeline

Participating centres and patient eligibility criteria

Data for the CVD-REAL study are sourced from several national databases (please click on the map above for further details), which all include a large number of patients with type 2 diabetes mellitus. Inclusion of the data in the study analysis is determined by the following criteria:

Inclusion criteria
  • Type 2 diabetes mellitus (diagnosed on or before the index date)
  • Aged 18 years or older on the index date
  • New user receiving or dispensed a prescription of an SGLT-2 inhibitor medication or another oral or injectable glucose-lowering drug, including fixed-dose combination products containing these medication groups
  • More than 1 year of data reported in the database before the index date
Exclusion criteria
  • Type 1 diabetes mellitus
  • Gestational diabetes in the year before the index date

Outcome measures

CVD-REAL 1 CVD-REAL 2

Primary outcome measures
  • Hospitalization for heart failure
Secondary outcome measures
  • All-cause mortality
  • Composite of hospitalisation for heart failure or all-cause mortality
Exploratory outcome measures
  • Acute myocardial infarction and atrial fibrillation

Primary outcome measures
  • All-cause mortality
Secondary outcome measures
  • Hospitalization for heart failure
  • Major cardiovascular events
  • Stroke
  • Myocardial infarction
  • Composite of all end points

Reference

1. Kosiborod et al. Circulation 2017;136:249–59

2. Data from the International Diabetes Federation Atlas, 8th edition

NCT02993614: Comparative effectiveness of cardiovascular outcomes in new users of SGLT-2 inhibitors (CVD-REAL) https://clinicaltrials.gov/ct2/show/NCT02993614.

More about CVD-REAL

For more information about the CVD-REAL study design, please visit the clinical trials registry website set up by the US National Institutes of Health at https://clinicaltrials.gov/ct2/show/NCT02993614.

Rationale

Type 2 diabetes mellitus affects millions of people worldwide and its prevalence is increasing. Diabetes is one of the leading causes of cardiovascular disease. Recent evidence indicates that some diabetes therapies are associated with both positive and negative cardiovascular effects. There is, therefore, an urgent need to improve understanding of the impact of newer classes of type 2 diabetes mellitus therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and SGLT-2 inhibitors, on cardiovascular outcomes in clinical practice.

Aim

CVD-REAL is a comparative effectiveness study that aims to compare new users of SGLT-2 inhibitors with new users of other glucose-lowering drugs with regard to hospitalization for heart failure and all-cause mortality. The study analysis is based on data from at least six countries: United States, United Kingdom, Germany, Sweden, Denmark and Norway.

Design

CVD-REAL is a multinational, retrospective, non-interventional, observational study spanning six countries across two continents (North America and Europe). The study will include data from approximately 1.4 million patients from the time they start treatment with an SGLT-2 inhibitor or other glucose-lowering drug to the end of the follow-up period. Depending on the launch date of the first SGLT-2 inhibitor in each participating country, this equates to a period of 4–5 years, as illustrated below.

CVD-REAL study timeline

Participating centres and patient eligibility criteria

Data for the CVD-REAL study are sourced from several national databases (please click here to see the full list of participating countries), which each include a large number of patients with type 2 diabetes mellitus. Inclusion of the data in the study analysis is determined by the following criteria.

Inclusion/exclusion criteria

Inclusion criteria
  • Type 2 diabetes mellitus (diagnosed on or before the index date)
  • Aged 18 years or older on the index date
  • New user receiving or dispensed a prescription of oral or injectable SGLT-2 inhibitor medication or other glucose-lowering drug, including fixed-dose combination products containing these medication groups
  • More than 1 year of data reported in the database before the index date
Exclusion criteria
  • Type 1 diabetes mellitus
  • Gestational diabetes within 1 year before the index date

Outcome measures

Primary outcome measure
  • Incidence of hospitalization for heart failure (from index date to 1 year) based on the hospitalization information obtained from general practice or hospital records, electronic health records or national health registers
Secondary outcome measures
  • Incidence of all-cause mortality (from index date to 1 year) based on the information obtained from national health registers
Exploratory outcome measures
  • Estimate the incidence of acute myocardial infarction and atrial fibrillation in both treatment groups

More about CVD-REAL

For more information about the CVD-REAL study design, please visit the clinical trials registry website set up by the US National Institutes of Health at www.clinicaltrials.gov.

NCT02993614: Comparative effectiveness of cardiovascular outcomes in new users of SGLT-2 inhibitors (CVD-REAL) https://clinicaltrials.gov/ct2/show/NCT02993614.