Empagliflozin and Cardiac Remodelling in People Without Diabetes
Condition: Cardiovascular Diseases; Left Ventricular Hypertrophy
MeSH terms: Cardiovascular Diseases; Hypertrophy, Left Ventricular; Hypertrophy
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the effects of empagliflozin on cardiac structure,
      function and circulating biomarkers in patients with cardiovascular risk factors, but without
      diabetes. Empagliflozin is an antihyperglycemic agent approved by Health Canada and the FDA
      for the treatment of type 2 diabetes. Previous post-marketing clinical trials demonstrated a
      reduction in cardiovascular deaths and heart failure in patients with type 2 diabetes treated
      with empagliflozin. In the first EMPA-HEART trial, we demonstrated that empagliflozin reduces
      cardiac mass in patients with type 2 diabetes, as seen through cardiac magnetic resonance
      imaging (cMRI). Therefore, the aim of this study, EMPA-HEART 2, is to determine whether
      empagliflozin can similarly impact cardiac structure in patients without diabetes, but with
      various cardiovascular risk factors.
    

Detailed description: 
      Sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, canagliflozin and
      dapagliflozin) are approved medications to improve glycemic control in adult patients with
      type 2 diabetes. When added to current standard-of-care diabetes treatment, SGLT2 inhibitors
      are associated with clinically meaningful reductions in major adverse cardiovascular events,
      reduced rates of hospitalization for heart failure and a decrease in major adverse kidney
      outcomes. Importantly, these benefits were observed consistently in people with and without
      type 2 diabetes and across all levels of baseline glycemic control. These data point towards
      a glucose-independent, cardioprotective effect of SGLT2 inhibition. How SGLT2 inhibition
      might reduce cardiac outcomes in people without diabetes remains unclear, and this is the
      specific objective of EMPA-HEART 2.

      The study drug, empagliflozin (marketed as Jardiance), belongs to a class of medications that
      lowers blood glucose (sugar) by preventing glucose from entering back into blood circulation
      and ensures it is eliminated in urine. Empagliflozin is approved by the FDA and Health Canada
      for the treatment of type 2 diabetes.

      This is a double-blind, randomized, placebo-controlled, parallel-group study of empagliflozin
      vs. placebo in patients without diabetes but with various cardiovascular risk factors. The
      purpose is to determine the effects of empagliflozin on cardiac structure by using cMRI.
      Patients who have given informed consent will undergo a baseline cMRI and will then be
      randomly assigned in a 1:1 basis to either empagliflozin 10 mg once daily or matching
      placebo. An end of study cMRI will be performed at 26 weeks (6 months after starting the
      study drug).

      The study subjects will be followed for 6 months. The patients will be assessed using cMRI,
      which is considered the "gold standard" for measuring left ventricular (LV) volume, mass, and
      ejection fraction. The investigators will assess changes from baseline in LV mass, LV
      end-diastolic volume, end-systolic volume, LV ejection fraction, LV diastolic and systolic
      function, and LV wall stress via cMRI in enrolled patients treated with empagliflozin
      compared to those who receive placebo. Additionally, changes from baseline in blood pressure,
      hematocrit, and biomarkers involved in the pathophysiology of heart failure, namely
      NT-proBNP, will be evaluated at 6 months.

      Study assessments and potential adverse events reporting will be undertaken at each study
      visit.
    

Intervention name(s): Empagliflozin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Single oral tablet; Placebo tablet manufactured to mimic empagliflozin 10 mg tablet
Other intervention name(s): Jardiance
Intervention MeSH terms: Empagliflozin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cardiovascular disease; Cardiac Magnetic Resonance Imaging; Sodium-Glucose Transporter 2 Inhibitors