Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™)

Cardiovascular Diabetology

Uli C Broedl²  Hans-Juergen Woerle²  Odd Erik Johansen⁵  Jennifer Newman⁸  Joan Kempthorne-Rawson⁸  Stefan Hantel⁴  Erich Bluhmki⁴  David Fitchett¹  Roberto Ferrari^1,10  Christoph Wanner⁷  John M Lachin⁶  Silvio E Inzucchi⁹  Bernard Zinman³ 

[1] Division of Cardiology, University of Toronto, Toronto, Canada;Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany;Division of Endocrinology, University of Toronto, Toronto, Canada;Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany;Boehringer Ingelheim Norway KS, Asker, Norway;The Biostatistics Center, The George Washington University, Rockville, MD, USA;Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg, Germany;Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA;Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA;Section of Cardiology, University of Ferrara, Ferrara, Italy

关键词: Type 2 diabetes;    SGLT2 inhibitor;    Microvascular;    Macrovascular;    Glycemic control;    Empagliflozin;    Body weight;    Blood pressure;   

Others  :  791663
DOI  :  10.1186/1475-2840-13-102

 received in 2014-05-15, accepted in 2014-06-13,  发布年份 2014

【 摘 要 】

Background

Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOME™ trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on macro-/microvascular outcomes.

Methods

Patients who were drug-naïve (HbA_1c ≥7.0% and ≤9.0%), or on background glucose-lowering therapy (HbA_1c ≥7.0% and ≤10.0%), and were at high risk of CV events, were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo (double blind, double dummy) superimposed upon the standard of care. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. CV events will be prospectively adjudicated by an independent Clinical Events Committee. The trial will continue until ≥691 confirmed primary outcome events have occurred, providing a power of 90% to yield an upper limit of the adjusted 95% CI for a hazard ratio of <1.3 with a one-sided α of 0.025, assuming equal risks between placebo and empagliflozin (both doses pooled). Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes (time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina pectoris) where non-inferiority is achieved.

Results

Between Sept 2010 and April 2013, 592 clinical sites randomized and treated 7034 patients (41% from Europe, 20% from North America, and 19% from Asia). At baseline, the mean age was 63 ± 9 years, BMI 30.6 ± 5.3 kg/m², HbA1c 8.1 ± 0.8%, and eGFR 74 ± 21 ml/min/1.73 m². The study is expected to report in 2015.

Discussion

EMPA-REG OUTCOME™ will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with the potential to show cardioprotection.

Trial registration

Clinicaltrials.gov NCT01131676

【 授权许可】

   
2014 Zinman et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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