Empagliflozin and Cardiac Remodelling in People Without Diabetes

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Michael's Hospital, Toronto; Unity Health Toronto
• Collaborators: Applied Health Research Centre; Boehringer Ingelheim; Canadian Medical and Surgical Knowledge Translation Research Group
• Treatments: Empagliflozin

Criteria

Inclusion Criteria:

1. Female Not of childbearing potential and male subjects ≥40 and ≤ 80 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 and ≤40 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. Indication of liver disease, defined by serum levels of either alanine-aminotransferase (ALT or SGPT), aspartate-aminotransaminase (AST or SGOT), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined at Visit 1

6. Hemoglobin < 90 g/L at Visit 1

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. BMI >40 kg/m2

15. Contraindications or inability to undergo magnetic resonance imaging such as the presence of metallic fragments, clips, or devices

16. Known history of infiltrative cardiomyopathy such as cardiac amyloidosis or cardiac sarcoidosis

17. Severe aortic stenosis

18. Severe aortic regurgitation

19. Severe mitral stenosis

20. Severe mitral regurgitation

21. Low voltage on ECG limb leads defined by the amplitude of the QRS complex in each limb lead ≤0.5 mV