The Cardiac Effects of Empagliflozin in Patients With High Risk of Heart Failure

Empagliflozin to Elderly and Obese Patients With Cardiovascular Disease (Empire Prevent: Cardiac): A Randomized Controlled Trial

The aim of this trial is to assess the effect of Empagliflozin on cardiac mass, volumes, cardiac biomarkers, metabolism, daily activity level, health-related quality of life in patients in elderly and obese patients with increased risk of developing heart failure. The primary hypotheses are that 180 days of treatment with Empagliflozin 10 mg a day will: 1) reduce left ventricular mass index, and 2) increase peak VO2 (maximal oxygen consumption) compared with placebo.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Obesity
• Intervention / Treatment: Drug: Empagliflozin 10 MG; Drug: Placebo

Detailed Description

The Empire Prevent: Cardiac is a part of the Empire Prevent Trial Program, which also comprises the Empire Prevent: Metabolic

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body mass index >28kg/m2
• Age 60-84 years
• Established risk factor for developing heart failure, defined as at least one of the following:
• hypertension
• ischemic heart disease
• stroke/transient cerebral ischemia
• chronic kidney disease (eGFR 30-45ml/min/1.73m2)

Exclusion Criteria:

• Diabetes mellitus type 1 or 2 (no medical history, no antidiabetic treatment)
• Heart failure with reduced ejection fraction (LVEF <40%)
• Inability to perform exercise test
• Dementia
• Severe non-compliance
• Substance abuse
• Severe chronic obstructive pulmonary disease (FEV1<50% expected value)
• Permanent atrial fibrillation
• GFR <30 ml/min/1,73m2
• Severe peripheral artery disease
• Cancer treatment within one year beside prostate cancer and basal cell carcinoma
• Severe aortic or mitral valve disease
• Pregnancy or breastfeeding
• Acute hospital admission within 30 days
• Participation in other pharmacological study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo matches the active drug in appearance, odor and labelling
Active Comparator: Empaglifloxin	Drug: Empagliflozin 10 MG; Patients are randomized 1:1 to receive either Empagliflozin or matching placebo for 180 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular mass index	Between-group difference in the change of left ventricular mass index (LVMI) assessed by cardiac magnetic resonance image	180 days
Maximal oxygen consumption	Between-group difference in the change of maximal oxygen consumption (peak VO2) assessed by cardiopulmonary exercise test	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily activity level	Between-group difference in the change of daily activity level assessed by accelerometer	180 days
Left ventricular function	Between-group difference in the change of first phase ejection fraction and left ventricular ejection fraction (LVEF) assessed by cardiac magnetic resonance image	180 days
Left ventricular volume	Between-group difference in the change of left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) assessed by cardiac magnetic resonance image	180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality-of-life scores	Between-group difference in the change of self-reported quality of life assessed by the 36-item short form health survey (SF-36 questionnaire). The SF-36 targets eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Each item is scored on a scale from 0 to 100, with a higher score representing a more favorable health state. An average score is calculated for each health concept.	180 days
Cardiac fibrosis	Between-group difference in the change of cardiac fibrosis assessed by cardiac magnetic resonance image	180 days
Blood pressure	Between-group difference in the change of systolic and diastolic blood pressure assessed by ambulatory blood pressure measurement	180 days
Wall stress	Between-group difference in the change of estimated end-systolic wall stress (ESWS). ESWS will be calculated from results of multimodality imaging combining MRI and echocardiography by using a formula incorporating MRI LV end-systolic diameter and wall thickness as well as echocardiographic mean and arterial blood pressure as proposed by Reichek et al. based on the Law of Laplace. (please see references Reichek et al and Carter-Storch et al. in the reference list)	180 days
Left atrium size	Between-group difference in the change of left atrial maximal and minimal size measured by cardiac magnetic resonance image	180 days
Left atrium function	Between-group difference in the change of left atrial emptying fraction and left atrium ejection fraction assessed by cardiac magnetic resonance image	180
Global strain	Between-group difference in the change of global strain assessed by cardiac magnetic resonance image	180 days
Biomarkers of heart disease	Between-group difference in the change of biomarkers of heart disease, including atrial natriuretic peptide (ANP), brain (B-type) natriuretic peptide (BNP), and N-terminal pro-hormone BNP (NT-proBNP). All measured as pmol/L.	180 days
Growth differentiation factor 15	Between-group difference in the change of the biomarker growth differentiation factor 15 (pg/ml)	180 days

Collaborators and Investigators

• Sponsor: Jacob Moller
• Collaborators: Rigshospitalet, Denmark; University Hospital Bispebjerg and Frederiksberg; Hillerod Hospital, Denmark; Herlev and Gentofte Hospital; Danish Heart Foundation
• Investigators: Principal Investigator: Jacob Eifer Møller, MD, PhD,, Odense University Hospital; Principal Investigator: Morten Schou, MD, PhD, DmSc, Herlev-Gentofte Hospital

Publications and helpful links

General Publications

• Reichek N, Wilson J, St John Sutton M, Plappert TA, Goldberg S, Hirshfeld JW. Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application. Circulation. 1982 Jan;65(1):99-108. doi: 10.1161/01.cir.65.1.99. No abstract available.
• Carter-Storch R, Moller JE, Christensen NL, Rasmussen LM, Pecini R, Sondergard E, Videbaek LM, Dahl JS. End-systolic wall stress in aortic stenosis: comparing symptomatic and asymptomatic patients. Open Heart. 2019 Apr 9;6(1):e001021. doi: 10.1136/openhrt-2019-001021. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2021
• Primary Completion (Actual): January 16, 2025
• Study Completion (Actual): January 16, 2025

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: S-20210028-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No