Heart FailurePhase 3NCT03332212

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

A Phase 3 study testing Empagliflozin in people with Heart Failure, run by Boehringer Ingelheim at 1 site in United Kingdom.

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 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 Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure
What is being tested?: Empagliflozin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 72 participants
Where: 1 siteUnited Kingdom
Study dates: 1 Mar 2018to 28 May 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

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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
NT-proBNP > 125pg/mL at screening in patient without AF or NT-pro-BNP > 600 pg/mL in patient with AF
Oral diuretics, if prescribed, should be stable for at least one week prior to Visit 1 and during screening period until Visit 2 (Randomisation).

Who cannot join

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

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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
Impaired renal function, defined as estimated Creatinine Clearance < 30 mL/min (using Cockcroft-Gault formula) or requiring dialysis, as determined at screening
Haemoglobin < 10 g/dL at screening
Type 1 Diabetes Mellitus (T1DM)
History of ketoacidosis
Major surgery (major according to the investigator's assessment) performed within 3 months prior to informed consent, or scheduled major elective surgery (e.g. hip replacement) within 3 months after Visit 1
Gastrointestinal (GI) surgery or GI disorder that could interfere with absorption of trial medication in the investigator's opinion
Any documented active or suspected malignancy or history of malignancy within 6 months prior to informed consent, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix or low risk prostate cancer (patients with pretreatment PSA <10 ng/mL, and biopsy Gleason score of ≤ 6 and clinical stage T1c or T2a)
Presence of any other disease than heart failure with a life expectancy of <1 year in the investigator's opinion
Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial
Patients with requirement for treatment with empagliflozin according to local standard of care
Treatment with any SGLT-2 inhibitor or combined SGLT-1 and 2 inhibitor within 1 week prior to informed consent or during screening period until Visit 2 (Randomisation)
Currently enrolled in another investigational device or drug study, or less than 30 days between randomisation and ending another investigational device or drug study, or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded.
Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors
Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
Women who are pregnant, breastfeeding, or who plan to become pregnant while in the trial
Any clinical condition that would jeopardise patients safety while participating in this trial, or may prevent the subject from adhering to the trial protocol

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

John Radcliffe Hospital
Oxford, OX3 9DU

Other trials in United Kingdom

About this study

Official title: 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

Conditions: Heart Failure
Being tested: Empagliflozin, Placebo
Medical subject headings: Heart Failure

What participants receive

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

EmpagliflozinDrug
Also called JARDIANCE, JARDIANZ, GIBTULIO
12 weeks
PlaceboDrug
Also called JARDIANCE, JARDIANZ, GIBTULIO
12 Weeks

Study groups in NCT03332212
Study group	Role	What they receive
Cohort A (Empagliflozin + Placebo)	Experimental	Heart Failure with Reduced Ejection Fraction Receives: Drug: Empagliflozin; Drug: Placebo
Cohort B (Empagliflozin + Placebo)	Experimental	Heart Failure with Preserved Ejection Fraction Receives: Drug: Empagliflozin; Drug: Placebo

What is being measured

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

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.
Measured: At baseline and at week 12.

Timeline

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

1 Mar 201828 May 2020

First posted6 Nov 2017
Study start1 Mar 2018
Primary completion21 May 2020
Study completion28 May 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heart FailureStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03332212
Sponsor's protocol ID: 1245-0148
Other IDs: 2017-000376-28, 2017
Status last verified: May 2021
First submitted: 2 Nov 2017
Last updated: 18 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 37070436
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.
PubMed 33960149

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Using Ultromics EchoGo HFpEF Algorithm to Identify and Treat High Heart Failure Risk in Patients With Type 2 Diabetes
Heart Failure, Diabetes
RecruitingObservational study
dPmax for Predicting Right Ventricular Failure After Left Ventricular Assist Device Implantation
Ventricular Dysfunction, Right
Active, not recruiting
Comparison of the Balloon-Expandable Edwards Valve and Self-Expandable CoreValve Evolut R or Evolut PRO System for the Treatment of Small, Severely Dysfunctional Surgical Aortic Bioprotheses. The 'LYTEN' Trial
Aortic Valve Stenosis, Regurgitation, Aortic
RecruitingObservational study
Norepinephrine in the Management of General Anesthesia-Induced Arterial Hypotension in Chronic Heart Failure Patients
Hypotension
Enrolling by invitationObservational study
Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
Heart Failure

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03332212
Acronym / sponsor ID: 1245-0148
Conditions: Heart Failure
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 72 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: 1 Mar 2018 (actual)
Primary completion: 21 May 2020 (actual)
Study completion: 28 May 2020 (actual)
First posted: 6 Nov 2017 (actual)
Results: Posted 18 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Cohort A (Empagliflozin + Placebo)	Experimental	Drug: Empagliflozin, Drug: PlaceboHeart Failure with Reduced Ejection Fraction
Cohort B (Empagliflozin + Placebo)	Experimental	Drug: Empagliflozin, Drug: PlaceboHeart Failure with Preserved Ejection Fraction

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

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

Key exclusion criteria (31 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EmpagliflozinAlso: JARDIANCE, JARDIANZ, GIBTULIO12 weeks	Drug	Cohort A (Empagliflozin + Placebo), Cohort B (Empagliflozin + Placebo)
PlaceboAlso: JARDIANCE, JARDIANZ, GIBTULIO12 Weeks	Drug	Cohort A (Empagliflozin + Placebo), Cohort B (Empagliflozin + Placebo)

Primary outcome

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.

Results and safety

Results posted to the registry on 18 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Cohort A	19	18
Placebo Cohort B	18	16
Empagliflozin 10mg Cohort A	17	17
Empagliflozin 10mg Cohort B	18	17

Primary outcome: 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.. Least squares mean (Standard Error). Unit: PCr / ATP Ratio

Measure	Placebo Cohort A n = 18	Placebo Cohort B n = 11	Empagliflozin 10mg Cohort A n = 17	Empagliflozin 10mg Cohort B n = 13
Value	0.068 (0.114)	0.259 (0.156)	-0.179 (0.117)	0.100 (0.143)

Placebo Cohort A vs Empagliflozin 10mg Cohort A: Mean Difference (Final Values): -0.247 (95% CI -0.582 to 0.087), p = 0.1418, ANOVA
Placebo Cohort B vs Empagliflozin 10mg Cohort B: Mean Difference (Final Values): -0.159 (95% CI -0.604 to 0.286), p = 0.4650, ANOVA

Population analysed: Per protocol set (PPS): The primary endpoint analysis was performed using the per protocol (PP) set of patients with valid PCr/ATP ratio measurements available at baseline and Week 12, and no important protocol violation relevant to the primary endpoint.

Adverse events

Time frame: All adverse events occurring between the start of treatment and end of the residual effect period, 7 days after the last dose of medication. Up to 95 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	7 of 36 (19.4%)	3 of 36 (8.3%)	0 of 36
Empagliflozin 10mg	1 of 35 (2.9%)	8 of 35 (22.9%)	0 of 35

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37070436Hundertmark 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.
Derived from this study: PubMed 33960149Hundertmark 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.
Related InfoLink provided by the sponsor.

Related trials for Heart Failure

Recruiting
Using Ultromics EchoGo HFpEF Algorithm to Identify and Treat High Heart Failure Risk in Patients With Type 2 Diabetes
Heart Failure, Diabetes
RecruitingObservational study
dPmax for Predicting Right Ventricular Failure After Left Ventricular Assist Device Implantation
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Comparison of the Balloon-Expandable Edwards Valve and Self-Expandable CoreValve Evolut R or Evolut PRO System for the Treatment of Small, Severely Dysfunctional Surgical Aortic Bioprotheses. The 'LYTEN' Trial
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Norepinephrine in the Management of General Anesthesia-Induced Arterial Hypotension in Chronic Heart Failure Patients
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Empagliflozin in people with Heart Failure, run by Boehringer Ingelheim at 1 site in United Kingdom.

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 17 inclusion and 31 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 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

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.). 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 NCT03332212, which also lists 2 linked publications.

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 18 Jun 2021.