Empagliflozin and Cardiac Remodelling in People Without Diabetes

NCT04461041 | Completed Phase 4 DMC

• 1 other identifier: 1245-0206
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Cardiovascular Diseases; Left Ventricular Hypertrophy

Keywords

Cardiovascular disease; Cardiac Magnetic Resonance Imaging; Sodium-Glucose Transporter 2 Inhibitors

Outcome Measures

Primary Outcomes (1)

• Left Ventricular (LV) mass

  Change in Left Ventricular (LV) mass (indexed to body surface area (BSA)) at 6 months. This will be measured using CMRI.

  6 months

Secondary Outcomes (9)

• LV end-diastolic volume

  6 months

• LV end-systolic volume

  6 months

• Left Ventricular Ejection Fraction (LVEF)

  6 months

• LV wall stress

  6 months

• LV systolic function

  6 months

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Single 10 mg tablet, administered orally once daily for 6 months

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Single 10 mg tablet, administered orally once daily for 6 months

Drug: Placebo

Interventions

Empagliflozin DRUG

Single oral tablet

Also known as: Jardiance

Empagliflozin

Placebo DRUG

Placebo tablet manufactured to mimic empagliflozin 10 mg tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)
• ≥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
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures

You may not qualify if:

• Female subjects who are pregnant, lactating or of childbearing potential, or are pre-menopausal
• Known type 1 or type 2 diabetes
• Hemoglobin A1C (A1C) ≥6.5%
• eGFR \<30 mL/min/1.73m2
• Known history of severe liver disease (e.g. Child Pugh Class B or C)
• Known history of severe symptomatic untreated anemia in the last 3 months (e.g. hemoglobin \< 90 g/L)
• 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.
• Systolic blood pressure \<95mmHg (as measured at the office/clinic visit)
• 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
• Significant allergy or known intolerance to SGLT2is or any ingredient in the formulations
• 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
• 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
• 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
• 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
• Known history of infiltrative cardiomyopathy such as cardiac amyloidosis or cardiac sarcoidosis

Sponsors & Collaborators

• Unity Health Toronto: lead
• Canadian Medical and Surgical Knowledge Translation Research Group: collaborator
• Boehringer Ingelheim: collaborator
• Applied Health Research Centre: collaborator

Study Sites (4)

Diagnostic Assessment Centre (AMS Diagnostics)

Toronto, Ontario, M1S 4N6, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

North York Diagnostic and Cardiac Centre

Toronto, Ontario, M6B 3H7, Canada

Location

Chang Gung Memorial Hospital

Keelung, Taiwan

Location

Related Publications (1)

• Connelly KA, Mazer CD, Puar P, Teoh H, Wang CH, Mason T, Akhavein F, Chang CW, Liu MH, Yang NI, Chen WS, Juan YH, Opingari E, Salyani Y, Barbour W, Pasricha A, Ahmed S, Kosmopoulos A, Verma R, Moroney M, Bakbak E, Krishnaraj A, Bhatt DL, Butler J, Kosiborod MN, Lam CSP, Hess DA, Rizzi Coelho-Filho O, Lafreniere-Roula M, Thorpe KE, Quan A, Leiter LA, Yan AT, Verma S. Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial. Circulation. 2023 Jan 24;147(4):284-295. doi: 10.1161/CIRCULATIONAHA.122.062769. Epub 2022 Nov 6.

  PMID: 36335517 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertrophy, Left Ventricular

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Subodh Verma, MD PhD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 8, 2020
• Study Start: April 1, 2021
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: February 17, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); TW (1)