Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors

NCT ID: NCT02993614

Last Updated: 2021-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

99999 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-11-30

Study Completion Date

2020-12-17

Brief Summary

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CVD-REAL is a multinational, observational cohort study in patients with type 2 diabetes mellitus evaluating the comparative effectiveness of initiating treatment with a sodium-glucose co-transporter-2 (SGLT-2) inhibitor versus another glucose-lowering drug. This study will compare the risk of all-cause mortality and clinically relevant cardiovascular (CV) outcomes respectively in patients who are new users of SGLT-2 inhibitors with those who are new users of other glucose-lowering drugs. CVD-REAL is aiming to collect data from approximately 4 million patients overall, from twelve countries across three major world regions.

Detailed Description

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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 the cases. Recent evidence indicates that certain glucose-lowering therapies are associated with reduction in cardiovascular outcomes. There is, therefore, an urgent need to improve the 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.

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 all-cause mortality and clinically relevant CV outcomes (including stroke, myocardial infarction, and hospitalization for heart failure) respectively. The study is based on data from 12 countries across four major world regions.

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. The study will collect data from approximately 4 million patients from the time they start treatment with a SGLT-2 inhibitor or another glucose-lowering drug (index date) to the end of the follow-up period.

The Study Population will consist of new users of SGLT-2i and other glucose lowering drugs respectively. These will be compared with all-cause mortality, hospitalization for heart failure, myocardial infarction and stroke during the follow-up period. In addition certain other cardiovascular and renal outcomes will be assessed descriptively in the two groups respectively.

The study period will range from launch of the first SGLT-2i in each of the countries and end at latest available data in each data source.

All-cause mortality and the incidence of cardiovascular events will be compared between new users of SGLT-2 inhibitors and the comparator arm using a hazard ratio (relative risk) and corresponding 95% confidence interval. The analysis will be performed using the Cox proportional hazards model or some other appropriate method.

Matching by propensity scores will be used to balance the potential confounding covariates between the SGLT-2i group and the reference group to ensure that the two groups are as similar as possible at baseline.To achieve sufficient power, a meta-analysis will be applied to integrate the point estimates from each of the individual database analyses and calculate an overall weighted estimate and corresponding 95% CI.

Conditions

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Diabetes Mellitus Type 2

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Inclusion Criteria

* New user receiving or dispensed prescription of SGLT-2i medication or other glucose lowering drug, oral as well as injectable, including fixed-dose combination (FDC) products containing these medication groups
* T2DM diagnosis on or prior to the index date
* ≥ 18 years old at index date
* \> 1 year data history in the database prior to the index date

Exclusion Criteria

* Patients with a T1DM diagnosis
* Patients with gestational diabetes within 1 year before index date
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Wilmington, Delaware, United States

Site Status

Research Site

Melbourne, D1690r00015, Australia

Site Status

Research Site

Mississauga, D1690r00015, Canada

Site Status

Research Site

Gentofte Municipality, D1690r00015, Denmark

Site Status

Research Site

Espoo, D1690r00015, Finland

Site Status

Research Site

Ulm, D1690r00015, Germany

Site Status

Research Site

Raanana, D1690r00015, Israel

Site Status

Research Site

Rome, D1690r00015, Italy

Site Status

Research Site

Tokyo, D1690r00015, Japan

Site Status

Research Site

Oslo, D1690r00015, Norway

Site Status

Research Site

Porto, D1690r00015, Portugal

Site Status

Research Site

Singapore, D1690r00015, Singapore

Site Status

Research Site

Seoul, D1690r00015, South Korea

Site Status

Research Site

Madrid, D1690r00015, Spain

Site Status

Research Site

Södertälje, D1690r00015, Sweden

Site Status

Research Site

Taipei, D1690r00015, Taiwan

Site Status

Research Site

Luton, D1690r00015, United Kingdom

Site Status

Countries

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United States Australia Canada Denmark Finland Germany Israel Italy Japan Norway Portugal Singapore South Korea Spain Sweden Taiwan United Kingdom

References

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Khunti K, Kosiborod M, Kim DJ, Kohsaka S, Lam CSP, Goh SY, Chiang CE, Shaw JE, Cavender MA, Tangri N, Franch-Nadal J, Holl RW, Jorgensen ME, Norhammar A, Eriksson JG, Zaccardi F, Karasik A, Magliano DJ, Thuresson M, Chen H, Wittbrodt E, Bodegard J, Surmont F, Fenici P; CVD-REAL Investigators and Study Group. Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data. Cardiovasc Diabetol. 2021 Jul 31;20(1):159. doi: 10.1186/s12933-021-01345-z.

Reference Type DERIVED
PMID: 34332558 (View on PubMed)

Nicolucci A, Candido R, Cucinotta D, Graziano G, Rocca A, Rossi MC, Tuccinardi F, Manicardi V. Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice. Adv Ther. 2019 Oct;36(10):2895-2909. doi: 10.1007/s12325-019-01043-z. Epub 2019 Aug 13.

Reference Type DERIVED
PMID: 31410779 (View on PubMed)

Cavender MA, Norhammar A, Birkeland KI, Jorgensen ME, Wilding JP, Khunti K, Fu AZ, Bodegard J, Blak BT, Wittbrodt E, Thuresson M, Fenici P, Hammar N, Kosiborod M; CVD-REAL Investigators and Study Group. SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL. J Am Coll Cardiol. 2018 Jun 5;71(22):2497-2506. doi: 10.1016/j.jacc.2018.01.085.

Reference Type DERIVED
PMID: 29852973 (View on PubMed)

Kosiborod M, Lam CSP, Kohsaka S, Kim DJ, Karasik A, Shaw J, Tangri N, Goh SY, Thuresson M, Chen H, Surmont F, Hammar N, Fenici P; CVD-REAL Investigators and Study Group. Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study. J Am Coll Cardiol. 2018 Jun 12;71(23):2628-2639. doi: 10.1016/j.jacc.2018.03.009. Epub 2018 Mar 11.

Reference Type DERIVED
PMID: 29540325 (View on PubMed)

Kosiborod M, Cavender MA, Fu AZ, Wilding JP, Khunti K, Holl RW, Norhammar A, Birkeland KI, Jorgensen ME, Thuresson M, Arya N, Bodegard J, Hammar N, Fenici P; CVD-REAL Investigators and Study Group*. Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation. 2017 Jul 18;136(3):249-259. doi: 10.1161/CIRCULATIONAHA.117.029190. Epub 2017 May 18.

Reference Type DERIVED
PMID: 28522450 (View on PubMed)

Other Identifiers

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D1690R00015

Identifier Type: -

Identifier Source: org_study_id

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