EMPA-VISION: A Randomised, Double-blind, Placebo-controlled, Mechanistic Cardiac Magnetic Resonance Study to Investigate the Effects of Empagliflozin Treatment on Cardiac Physiology and Metabolism in Patients With Heart Failure

Boehringer Ingelheim1 site in 1 country72 target enrollmentMarch 1, 2018

ConditionsHeart Failure

InterventionsEmpagliflozin Placebo

DrugsEmpagliflozin Placebo

Overview

Phase: Phase 3
Intervention: Empagliflozin
Conditions: Heart Failure
Sponsor: Boehringer Ingelheim
Enrollment: 72
Locations: 1
Primary Endpoint: Change From Baseline to Week 12 in PCr/ATP Ratio in the Resting State Measured by 31P Cardiac Magnetic Resonance Spectroscopy (MRS).
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The objective of this trial is to assess the effect of empagliflozin on cardiac physiology and metabolism aiming to provide a scientific explanation of the underlying mechanism by which empagliflozin improves HF related outcomes in patients with chronic heart failure

Registry

clinicaltrials.gov

Start Date

March 1, 2018

End Date

May 28, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Chronic heart failure diagnosed at least 3 months before informed consent
•NYHA class II-IV at screening
•Age ≥ 18 years at screening
•Male or female patients. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
•Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
•Cohort A Heart Failure with Reduced Ejection Fraction (HFrEF)
•Left ventricular ejection fraction (LVEF) ≤ 40% as measured by ECHO at screening
•The following signs of heart failure;
•Elevated NT-proBNP (\>125 pg/mL) at screening in patient without atrial fibrillation (AF)
•Elevated NT-proBNP (\>600 pg/mL) at screening in patient with AF

Exclusion Criteria

•Stroke or transient ischaemic attack (TIA) within 6 months prior to informed consent.
•Any patients with myocardial scars and/or non-viable myocardium in the interventricular septum, unstable angina due to significant coronary artery disease (CAD), or major (in the opinion of the investigator) cardiovascular surgery.
•Any contraindication for MRI, CPET and/or dobutamine stress test in accordance with the institution guidance, including implanted left ventricular assist device (LVAD),implantable cardioverter defibrillator (ICD), cardiac resynchronisation therapy (CRT) or any cardiac device.
•Heart transplant recipient or listed for heart transplant
•Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction
•Moderate to severe uncorrected valvular heart disease, obstructive or regurgitant, or any valvular heart disease expected to lead to surgery in the Investigator's opinion
•Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or LVAD or hospitalisation within 1 week prior to Visit 1 (Screening), or during screening period until Visit 2 (Randomisation)
•Systolic blood pressure (SBP) ≥ 180 mmHg at screening. If SBP \>150 mmHg and \<180mmHg at screening, the patient is ineligible if receiving 3 or more antihypertensive drugs
•Symptomatic hypotension and/or a SBP \< 100 mmHg at Screening
•Atrial fibrillation which is uncontrolled in the opinion of the investigator

Arms & Interventions

Cohort A (Empagliflozin + Placebo)

Heart Failure with Reduced Ejection Fraction

Intervention: Empagliflozin

Cohort A (Empagliflozin + Placebo)

Heart Failure with Reduced Ejection Fraction

Intervention: Placebo

Cohort B (Empagliflozin + Placebo)

Heart Failure with Preserved Ejection Fraction

Intervention: Empagliflozin

Cohort B (Empagliflozin + Placebo)

Heart Failure with Preserved Ejection Fraction

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline to Week 12 in PCr/ATP Ratio in the Resting State Measured by 31P Cardiac Magnetic Resonance Spectroscopy (MRS).

Time Frame: At baseline and at week 12.

The primary endpoint of efficacy was the change from baseline to Week 12 in phosphocreatine/adenosine triphosphate (PCr/ATP) ratio in the resting state measured by 31P cardiac magnetic resonance spectroscopy (MRS). Adjusted mean values were calculated using an analysis of variance (ANOVA) model, with treatment, history of diabetes, and history of atrial fibrillation (AF) as fixed effects.