NCT04461041

Empagliflozin and Cardiac Remodelling in People Without Diabetes

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 169 (actual)
• Sponsor: Unity Health Toronto · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Cardiovascular Diseases
• Left Ventricular Hypertrophy

Interventions

Type	Name	Description
DRUG	Empagliflozin	Single oral tablet
DRUG	Placebo	Placebo tablet manufactured to mimic empagliflozin 10 mg tablet

Timeline

• Start date: 2021-04-01
• Primary completion: 2022-07-31
• Completion: 2022-07-31
• First posted: 2020-07-08
• Last updated: 2023-02-17

Locations

4 sites across 2 countries: Canada, Taiwan