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Cardiovascular DiseasesPhase 4EMPA-HEART 2NCT04461041

Empagliflozin and Cardiac Remodelling in People Without Diabetes

A Phase 4 study testing Empagliflozin in people with Cardiovascular Diseases and Left Ventricular Hypertrophy, run by Unity Health Toronto at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Empagliflozin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
169 participants
Where
4 sitesin 2 countries
Study dates
1 Apr 2021to 31 Jul 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 12Show fewer
  • 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

Who cannot join

  • 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)
Show all 20Show fewer
  • 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
  • Severe aortic stenosis
  • Severe aortic regurgitation
  • Severe mitral stenosis
  • Severe mitral regurgitation
  • Low voltage on ECG limb leads defined by the amplitude of the QRS complex in each limb lead ≤0.5 mV

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Canada3 sites

  • Diagnostic Assessment Centre (AMS Diagnostics)

    Toronto, Ontario, M1S 4N6

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

  • North York Diagnostic and Cardiac Centre

    Toronto, Ontario, M6B 3H7

Other trials in Canada

Taiwan1 site

  • Chang Gung Memorial Hospital

    Keelung

Other trials in Taiwan

About this study

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.

Read the 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.

Being tested
Empagliflozin, Placebo
Keywords
Cardiovascular disease, Cardiac Magnetic Resonance Imaging, Sodium-Glucose Transporter 2 Inhibitors
Medical subject headings
Cardiovascular Diseases, Hypertrophy, Left Ventricular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EmpagliflozinDrug

    Also called Jardiance

    Single oral tablet

  • PlaceboDrug

    Placebo tablet manufactured to mimic empagliflozin 10 mg tablet

Study groups in NCT04461041
Study groupRoleWhat they receive
EmpagliflozinActive comparatorSingle 10 mg tablet, administered orally once daily for 6 months
Receives: Drug: Empagliflozin
PlaceboPlacebo comparatorSingle 10 mg tablet, administered orally once daily for 6 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (9)

  1. LV end-diastolic volume

    Change in LV end-diastolic volume (indexed to BSA) at 6 months. This will be measured using CMRI.

    Measured: 6 months

  2. LV end-systolic volume

    Change in LV end-systolic volume (indexed to BSA) at 6 months. This will be measured using CMRI.

    Measured: 6 months

  3. Left Ventricular Ejection Fraction (LVEF)

    Change in LVEF at 6 months. This will be measured using CMRI.

    Measured: 6 months

  4. LV wall stress

    Change in LV wall stress at 6 months. This will be measured using CMRI.

    Measured: 6 months

  5. LV systolic function

    Change in LV systolic function at 6 months. This will be measured using CMRI.

    Measured: 6 months

  6. LV diastolic function

    Change in LV diastolic function at 6 months. This will be measured using CMRI.

    Measured: 6 months

  7. NT-proBNP

    Change in circulating NT-proBNP at 6 months.

    Measured: 6 months

  8. Systolic and diastolic blood pressure

    Change in systolic and diastolic blood pressure at 6 months.

    Measured: 6 months

  9. Hematocrit

    Change in hematocrit at 6 months in patients.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2020
  2. Study start1 Apr 2021
  3. Primary completion31 Jul 2022
  4. Study completion31 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04461041
Sponsor's protocol ID
1245-0206
Acronym
EMPA-HEART 2
Status last verified
Feb 2023
First submitted
2 Jul 2020
Last updated
17 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36335517

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Empagliflozin in people with Cardiovascular Diseases and Left Ventricular Hypertrophy, run by Unity Health Toronto at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Left Ventricular (LV) mass (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04461041, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2023.

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