A Randomized, Double-blind, Double-dummy, Multi-center Study to Assess Safety and Efficacy of Different Oral Doses of BAY94-8862 in Subjects With Emergency Presentation at the Hospital Because of Worsening Chronic Heart Failure With Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Chronic Kidney Disease Alone Versus Eplerenone
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Bayer
- Enrollment
- 1,066
- Primary Endpoint
- Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90
Study Overview
Brief Summary
To assess a new drug, BAY94-8862, given orally at different doses, to evaluate whether it was safe and can help the well-being of patients with worsening chronic heart failure and either type II diabetes with or without chronic kidney disease or kidney disease alone. These treatment doses were compared to eplerenone, another marketed drug approved to treat heart failure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Men and women aged 18 years and older. The lower age limit may be higher if legally required in the participating country
- •Women of childbearing potential can only be included in the study if a pregnancy test is negative and if they agree to use adequate contraception when sexually active
- •Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital
- •Subjects with clinical diagnosis of chronic heart failure (CHF) either ischemic or non ischemic, New York Heart Association (NYHA) functional class II-IV
- •Subjects with type 2 diabetes mellitus and / or
- •Subjects with 30 mL/min/1.73m^2 </= eGFR </= 60 mL/min/1.73m^2 (MDRD, Modification of Diet in Renal Disease Study Group) at screening
- •Left ventricular ejection fraction (LVEF) </= 40%
- •Blood potassium </= 5.0 mmol/L at screening
- •Systolic blood pressure >/= 90 mmHg without signs and symptoms of hypotension at the screening visit
Exclusion Criteria
- •Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
- •Acute coronary syndrome (ACS) in last 30 days prior to screening
- •Cardiogenic shock
- •Valvular heart disease requiring surgical intervention during the course of the study
- •Stroke or transient ischemic cerebral attack in the last 3 months prior to the screening visit
- •Concomitant treatment with any mineralocorticoid receptor antagonist (MRA), renin inhibitor, or potassium-sparing diuretic
Arms & Interventions
Finerenone(BAY94-8862)[2.5mg] + Placebo
Oral - 2.5mg once daily (OD) for 30 days. Potential up-titration to 5mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Placebo (Drug)
Finerenone (BAY94-8862)[5mg] + Placebo
Oral - 5mg OD for 30 days. Potential up-titration to 10 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Placebo (Drug)
Finerenone (BAY94-8862)[7.5mg] + Placebo
Oral - 7.5mg OD for 30 days. Potential up-titration to 15 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Placebo (Drug)
Finerenone (BAY94-8862)[10mg] + Placebo
Oral - 10mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Finerenone (BAY94-8862) (Drug)
Finerenone (BAY94-8862)[10mg] + Placebo
Oral - 10mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Placebo (Drug)
Finerenone (BAY94-8862)[15mg] + Placebo
Oral - 15mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Placebo (Drug)
Eplerenone [25 mg] + Placebo
Oral - 25mg every other day (EOD). Potential up-titration to 25mg OD after 30 days and 50mg OD after 60 days.Placebo OD for 90 days.
Intervention: Placebo (Drug)
Eplerenone [25 mg] + Placebo
Oral - 25mg every other day (EOD). Potential up-titration to 25mg OD after 30 days and 50mg OD after 60 days.Placebo OD for 90 days.
Intervention: Inspra (eplerenone) (Drug)
Finerenone (BAY94-8862)[15mg] + Placebo
Oral - 15mg OD for 30 days. Potential up-titration to 20 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Finerenone (BAY94-8862) (Drug)
Finerenone (BAY94-8862)[5mg] + Placebo
Oral - 5mg OD for 30 days. Potential up-titration to 10 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Finerenone (BAY94-8862) (Drug)
Finerenone(BAY94-8862)[2.5mg] + Placebo
Oral - 2.5mg once daily (OD) for 30 days. Potential up-titration to 5mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Finerenone (BAY94-8862) (Drug)
Finerenone (BAY94-8862)[7.5mg] + Placebo
Oral - 7.5mg OD for 30 days. Potential up-titration to 15 mg OD after 30 days or 60 days. Treatment duration 90 days. Placebo OD for 90 days.
Intervention: Finerenone (BAY94-8862) (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With a Relative Decrease in NT-proBNP of More Than 30% From Baseline to Day 90
Time Frame: Baseline and Day 90
N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute and chronic heart failure (CHF) and may be useful to establish prognosis in heart failure.
Secondary Outcomes
- Number of Participants With Emergency Presentations for Worsening Chronic Heart Failure (WCHF)(Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120))
- Number of Participants With Death Due to Any Cause(Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120))
- Change From Baseline in KCCQ Questionnaire Scores at Specified Visits(Baseline, Day 30 and Day 90)
- Number of Participants With Cardiovascular Hospitalization(Day 30, Day 60, Day 90 and Follow-up (30 days post-last dose, assessed up to Day 120))
- Ratio of BNP at Specified Visits to BNP at Baseline(Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120))
- Ratio of NT-proBNP at Specified Visits to NT-proBNP at Baseline(Day 30, Day 60, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120))
- Change From Baseline in EQ-5D-3L Questionnaire Scores at Specified Visits(Baseline, Day 30, Day 90, Premature discontinuation (only for participants who have discontinued the study prematurely, to be performed as soon as possible after withdrawal of study drug) and Follow-up (30 days post-last dose, assessed up to Day 120))