EASi-HF Reduced - A Phase III Double-blind, Randomised, Parallel-group Superiority Trial to Evaluate Efficacy and Safety of the Combined Use of Oral Vicadrostat (BI 690517) and Empagliflozin Compared With Placebo and Empagliflozin in Participants With Symptomatic Chronic Heart Failure (HF: NYHA II-IV) and Left Ventricular Ejection Fraction (LVEF) < 40%

Plain English Summary

A Study to Test Whether Vicadrostat (BI 690517) in Combination With Empagliflozin Helps People With Heart Failure and a Weak Pumping Function of the Left Side of the Heart is a Phase 3 clinical trial sponsored by Boehringer Ingelheim studying Heart Failure. Tests if combining vicadrostat and empagliflozin helps people with chronic heart failure and weak left ventricle function. For adults with chronic heart failure (NYHA II-IV) and LVEF < 40% for at least 3 months. Participation involves taking study medicines (vicadrostat/empagliflozin or placebo/empagliflozin) daily for up to 3.5 years, with regular visits and health checks. Alternatives include standard heart failure treatments, but this trial aims to improve outcomes. The trial aims to enroll 4200 participants.

Official Summary

This study is open to adults with chronic heart failure (HF) who have a reduced left ventricular ejection fraction (LVEF) of less than 40%. People can join the study if they have been diagnosed with chronic HF at least 3 months before they start on the study. The purpose of this study is to find out whether a medicine called vicadrostat, in combination with another medicine called empagliflozin, helps people with chronic heart failure. In this study, participants are put into 2 groups randomly. Participants have an equal chance of being in either group. One group takes vicadrostat/empagliflozin tablets, and the other group takes placebo/empagliflozin tablets. Placebo tablets look like vicadrostat tablets but do not contain any medicine. Participants take the study medicines as tablets once a day for between about 6 months and about 3.5 years. During this time, they can continue their regular treatment for heart failure. Participants can stay in the study as long as they benefit from treatment and can tolerate it, for a maximum of about 3.5 years. During this time, they visit the study site regularly. The exact number of visits is different for each participant, depending on how long they stay in the study. The study staff may also contact the participants by phone for some visits. Participants also regularly answer questions about their well-being. The doctors document when participants experience worsening of their heart failure symptoms, go to hospital due to heart failure or die during the study. The time until these events are observed is compared between the two treatment groups to see whether the treatment works. The doctors also regularly check participants' health and take note of any unwanted effects.

Who Can Participate

Here is what you need to know about eligibility for this trial. 18+ years old, diagnosed with chronic heart failure for at least 3 months, LVEF < 40%. Women of childbearing potential must use effective birth control. No recent major surgery, heart transplant, or specific heart conditions. Cannot be taking certain medications or treatments. This trial is studying Heart Failure, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the time to first event of cardiovascular death, hospitalization for heart failure, or urgent heart failure visit. The specific primary outcome measures are: Time to first event of Cardiovascular (CV) death, or Hospitalisation for heart failure (HHF), or Urgent heart failure (HF) visit (up to 43 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a gap in treatment options for people with chronic heart failure and weak left ventricle function. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Heart Failure, where improved treatment options are needed.

Investor Insight

Market size is large, with a competitive landscape focused on improving heart failure treatments. Approval probability is moderate given the phase and sponsor. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 4200 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have chronic heart failure and LVEF < 40% for at least 3 months. Participation involves taking study medicines daily and regular visits to the study site. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 4,200 participants

Interventions

• DRUG: vicadrostat — vicadrostat
• DRUG: empagliflozin — empagliflozin
• DRUG: Placebo — Placebo matching vicadrostat

Primary Outcomes

• Time to first event of Cardiovascular (CV) death, or Hospitalisation for heart failure (HHF), or Urgent heart failure (HF) visit (up to 43 months)

Secondary Outcomes

• Key secondary endpoint: Time to first event of cardiovascular death or HHF (up to 43 months)
• Key secondary endpoint: Occurrences of HHF (first and recurrent) (up to 43 months)
• Key secondary endpoint: Absolute change from baseline in Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week 32 (at baseline, at week 32)
• Key secondary endpoint: Time to cardiovascular death (up to 43 months)
• Key secondary endpoint: Time to all-cause mortality (up to 43 months)

Full Eligibility Criteria

Inclusion criteria:

1. At least 18 years old and at least at the legal age of consent in countries where it is greater than 18 years
2. Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
3. Male or female participants. 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 and instructions on the duration of their use is provided in the protocol.
4. Chronic heart failure (HF) diagnosed at least 3 months before Visit 1, and in New York Heart Association (NYHA) classes II to IV at Visit 1, with left ventricular ejection fraction (LVEF) \< 40% per local reading (obtained by echocardiography, radionuclide ventriculography, invasive angiography, magnetic resonance imaging (MRI), or computed tomography (CT)).
5. Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) at Visit 1, analysed at the central laboratory
6. Treated according to best possible standard of care (SOC) (disregarding sodium-dependent glucose co-transporter 2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA)) in accordance with applicable heart failure (HF) local/international guidelines and judgement of the investigator.

Additional inclusion criteria apply.

Exclusion criteria:

1. Treatment with an MRA (e.g. spironolactone, eplerenone, finerenone) within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator. Treatment with an MRA should not be discontinued with the intention of study enrolment.
2. Treatment with amiloride or other potassium-sparing diuretic within 14 days prior to Visit 1 or requiring such treatment before randomisation or planned during the trial based on the judgment of the investigator.
3. Receiving the following treatments:

   * A direct renin inhibitor (e.g. aliskiren) at Visit 2
   * More than one angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNi) used simultaneously at Visit 2
   * Other aldosterone synthase inhibitors, e.g. baxdrostat at Visit 2 or planned during the trial
   * Systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) at Visit 2
   * In case of acute decompensated HF:

     * i.v. inotrope, i.v. vasodilating drug (e.g. nitrate, nitroprusside), or i.v. natriuretic peptide (e.g. nesiritide, carperitide), or mechanical support (e.g. intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, any ventricular assist device) within 24 hours prior to randomisation
     * i.v. diuretic with a dose that has been increased/intensified within 6 hours prior to randomisation (a stable dose of an i.v. diuretic is not exclusionary)
4. Myocardial infarction (MI), transient ischemic attack (TIA), stroke, coronary artery bypass graft surgery (CABG), heart valve surgery/intervention or any other major surgery (major according to the investigator's assessment) within 90 days prior to Visit 2, or scheduled for major elective surgery (e.g. hip replacement, CABG)
5. Percutaneous coronary intervention (PCI) or any angiography using iodinated contrast agents in the 7 days prior to Visit 2
6. Heart transplant recipient, awaiting heart transplant, or currently implanted left ventricular assist device (LVAD)
7. Known cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, hypertrophic obstructive cardiomyopathy or known pericardial constriction, or cardiomyopathy with potentially reversible cause such as stress or peripartum cardiomyopathy or cardiomyopathy induced by chemotherapy within 12 months prior to Visit 1 and until Visit 2
8. Acute inflammatory heart disease, such as acute myocarditis, within 90 days preceding prior to Visit 1 and until Visit 2 Further exclusion criteria apply.

Trial Locations

• Alliance for Multispecialty Research, LLC, Mobile, Alabama, United States
• Drug Research and Analysis Corporation, Montgomery, Alabama, United States
• Cure Clinical Research, Beverly Hills, California, United States
• Valley Clinical Trials, Inc., Covina, California, United States
• North Coast Cardiology, Encinitas, California, United States
• Orange County Research Center, Lake Forest, California, United States
• Merced Vein and Vascular Center, Merced, California, United States
• Radin Cardiovascular Medical Group, Newport Beach, California, United States
• Amicis Research Center - Nordhoff, Northridge, California, United States
• University of California San Diego, San Diego, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Chronic heart failure, left ventricular ejection fraction (LVEF) < 40%, heart failure with reduced ejection fraction (HFrEF), cardiomyopathy, myocarditis.

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