Phase IIb Safety and Efficacy Study of Different Oral Doses of BAY94-8862 in Subjects With Worsening Chronic Heart Failure and Left Ventricular Systolic Dysfunction and Either Type 2 Diabetes Mellitus With or Without Chronic Kidney Disease or Chronic Kidney Disease Alone (ARTS-HF)

Bayer

Status and phase: Completed; Phase 2

Conditions: Heart Failure

Treatments: Drug: Placebo; Drug: Finerenone (BAY94-8862); Drug: Inspra (eplerenone)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01807221

2012-002627-15 (EudraCT Number)

14564

Details and patient eligibility

About

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.

Enrollment: 1,066 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,066 participants in 6 patient groups

Finerenone(BAY94-8862)[2.5mg] + Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Finerenone (BAY94-8862)

Finerenone (BAY94-8862)[5mg] + Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Finerenone (BAY94-8862)

Finerenone (BAY94-8862)[7.5mg] + Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Finerenone (BAY94-8862)

Finerenone (BAY94-8862)[10mg] + Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Finerenone (BAY94-8862)

Finerenone (BAY94-8862)[15mg] + Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Finerenone (BAY94-8862)

Eplerenone [25 mg] + Placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Inspra (eplerenone)