Empagliflozin and Cardiac Remodelling in People Without Diabetes

1245-0206

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.

2021-04-01

2022-07-31

2022-07-31

Completed

Early phase I

169

Inclusion Criteria: 1. Female Not of childbearing potential and male subjects ≥ 18 and ≤ 85 years of age (Women Not of childbearing potential are females who are permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause or ≥6 weeks post-surgical bilateral oophorectomy prior to Screening.) 2. ≥1 of the major criteria or ≥2 of the minor criteria below: Major criteria * Increased LVMi of ≥96 g/m2 for women and ≥116 g/m2 for men (as calculated by echocardiogram); or LVMi ≥81 g/m2 for women and ≥85 g/m2 for men (as calculated by cMRI) * ECG evidence of LV hypertrophy (as per the Sokolow-Lyon criteria) * Structural heart disease defined as interventricular septal thickness or posterior wall thickness at end-diastole of ≥11 mm (as measured by 2D echocardiography or cMRI) * Persistent hypertension (defined as office blood pressure ≥140/90 mmHg) despite being on ≥3 antihypertensive medications Minor criteria * Prior history of a myocardial infarction (≥3 months ago) * eGFR ≥30 and ≤60 mL/min/1.73 m2 (as measured by the CKD-EPI formula) * Body mass index (BMI) ≥27 kg/m2 3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures Exclusion Criteria: 1. Female subjects who are pregnant, lactating or of childbearing potential, or are pre-menopausal 2. Known type 1 or type 2 diabetes 3. Hemoglobin A1C (A1C) ≥6.5% 4. eGFR \<30 mL/min/1.73m2 5. Known history of severe liver disease (e.g. Child Pugh Class B or C) 6. Known history of severe symptomatic untreated anemia in the last 3 months (e.g. hemoglobin \< 90 g/L) 7. History of ketoacidosis, or increased chance of developing diabetic ketoacidosis (DKA) e.g. patients who suffer from excessive vomiting, diarrhea, or sweating; subjects who are on a very low carbohydrate diet; or subjects who drink a lot of alcohol. 8. Systolic blood pressure \<95mmHg (as measured at the office/clinic visit) 9. Subjects in whom coronary revascularization by either percutaneous coronary intervention or bypass surgery is being contemplated within the next 6 months, or who have undergone coronary revascularization in the prior 3 months 10. Significant allergy or known intolerance to SGLT2is or any ingredient in the formulations 11. Subjects currently experiencing any clinically significant or unstable medical condition that in the opinion of the investigator might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease, and psychiatric disease 12. Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening 13. Subjects who have participated in other interventional studies which may affect any of the primary or secondary outcomes of the study within 30 days of the screening visit 14. Contraindications or inability to undergo magnetic resonance imaging such as severe obesity (e.g. weight \>500 lbs) or the presence of metallic fragments, clips, or devices 15. Known history of infiltrative cardiomyopathy such as cardiac amyloidosis or cardiac sarcoidosis 16. Severe aortic stenosis 17. Severe aortic regurgitation 18. Severe mitral stenosis 19. Severe mitral regurgitation 20. Low voltage on ECG limb leads defined by the amplitude of the QRS complex in each limb lead ≤0.5 mV

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2023-02-17