A Study That Looks at the Function of the Heart in Patients With Heart Failure Who Take Empagliflozin

NCT03332212 | Completed Phase 3 Results

• 2 other identifiers: 1245-01482017-000376-28
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

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

  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.

  At baseline and at week 12.

Study Arms (2)

Cohort A (Empagliflozin + Placebo)

EXPERIMENTAL

Heart Failure with Reduced Ejection Fraction

Drug: Empagliflozin; Drug: Placebo

Cohort B (Empagliflozin + Placebo)

EXPERIMENTAL

Heart Failure with Preserved Ejection Fraction

Drug: Empagliflozin; Drug: Placebo

Interventions

Empagliflozin DRUG

12 weeks

Also known as: JARDIANCE, JARDIANZ, GIBTULIO

Cohort A (Empagliflozin + Placebo); Cohort B (Empagliflozin + Placebo)

Placebo DRUG

12 Weeks

Also known as: JARDIANCE, JARDIANZ, GIBTULIO

Cohort A (Empagliflozin + Placebo); Cohort B (Empagliflozin + Placebo)

Eligibility Criteria

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

You may qualify if:

• 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
• Appropriate dose of medical therapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine) consistent with prevailing local and international HF guidelines, stable for at least one week prior to Visit 1 and during screening period until Visit 2 (Randomisation) with the exception of diuretics which must be stable for at least one week prior to Visit 2 to control symptoms. If required, the investigator must document in the source documents the reason why the patient is not on the target dose per local guidelines.
• Cohort B Heart Failure with Preserved Ejection Fraction (HFpEF)
• Left ventricular ejection fraction (LVEF) ≥ 50% as measured by ECHO at screening and no previous measurement of LVEF ≤ 40%.
• The following combined signs of heart failure;
• Structural heart disease (LA enlargement \[LAVI \>34 mL/m2\] and/or LVH \[LVMI ≥ 115 g/m2 for males and ≥ 95 g/m2 for females\]) by ECHO at screening or within 3 months prior to informed consent AND

You may not qualify if:

• 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
• Untreated ventricular arrhythmia with syncope documented within the 3 months prior to informed consent in patients without ICD
• Diagnosis of cardiomyopathy induced by chemotherapy or peripartum within the 12 months prior to informed consent
• Symptomatic bradycardia or second or third degree heart block in need of a pacemaker after adjusting beta-blocker therapy or any other negative inotropic agents, if appropriate
• Chronic pulmonary disease requiring home oxygen, oral steroid therapy or hospitalisation for exacerbation within 12 months prior to informed consent, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension
• Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT),or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at screening

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• Hundertmark MJ, Adler A, Antoniades C, Coleman R, Griffin JL, Holman RR, Lamlum H, Lee J, Massey D, Miller JJJJ, Milton JE, Monga S, Mozes FE, Nazeer A, Raman B, Rider O, Rodgers CT, Valkovic L, Wicks E, Mahmod M, Neubauer S. Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial. Circulation. 2023 May 30;147(22):1654-1669. doi: 10.1161/CIRCULATIONAHA.122.062021. Epub 2023 Apr 18.

  PMID: 37070436 DERIVED

• Hundertmark MJ, Agbaje OF, Coleman R, George JT, Grempler R, Holman RR, Lamlum H, Lee J, Milton JE, Niessen HG, Rider O, Rodgers CT, Valkovic L, Wicks E, Mahmod M, Neubauer S. Design and rationale of the EMPA-VISION trial: investigating the metabolic effects of empagliflozin in patients with heart failure. ESC Heart Fail. 2021 Aug;8(4):2580-2590. doi: 10.1002/ehf2.13406. Epub 2021 May 6.

  PMID: 33960149 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Due to the suspension of face-to-face contact imposed in March 2020 to restrict transmission of COVID-19, the number of patients included in the analysis of efficacy for the Heart failure with preserved ejection fraction was substantially reduced, which meant that this cohort was also under powered (reduced from 80% to 70%) for the planned analysis of the primary endpoint.

Results Point of Contact

• Title: Boehringer Ingelheim , Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 6, 2017
• Study Start: March 1, 2018
• Primary Completion: May 21, 2020
• Study Completion: May 28, 2020
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Locations

GB (1)