Phase IIb safety and efficacy study of different oral doses of BAY 94-8862 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 moderate chronic kidney disease alone

Conditions: Subjects with worsening chronic heart failure (WCHF) and left ventricular systolic dysfunction and either type 2 diabetes mellitus (DM type 2) with or without chronic kidney disease (CKD) or moderate chronic kidney disease alone
MedDRA version: 17.0Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857
MedDRA version: 17.0Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861
MedDRA version: 17.0Level: LLTClassification code 10066498Term: Cardiac failure chronic aggravatedSystem Organ Class: 100000004849
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2012-002627-15-AT

Lead Sponsor: Bayer HealthCare AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1510

Inclusion Criteria

• Men and women aged 18 years and older. The lower age limit may be higher if legally requested 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 a adequate contraception when sexually active. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of wihich at least one is a physical barrier (eg. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices)
• Subjects with worsening chronic heart failure requiring emergency presentation to hospital and treatment with intravenous diuretics at hospital
• Subjects with clinical diagnosis of CHF either ischemic or non ischemic, NYHA functional class II -IV
• Subjects with type 2 diabetes mellitus
and / or
Subjects with 30 mL/min/1.73m2 < or = eGFR < or = 60 mL/min/1.73m2 (MDRD)(23) at screening
• Left ventricular ejection fraction (LVEF) < or = 40%
• Serum potassium < or = 5.0 mmol/L at screening
• Systolic blood pressure > or = 90 mmHg without signs and symptoms of hypotension at the screening visit

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1110

Exclusion Criteria

• Acute de-novo heart failure or acute inflammatory heart disease, e.g. acute myocarditis
• Acute coronary syndrome (ACS) in the 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 MRA, renin inhibitor, or potassium-sparing diuretic

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective of the study is to investigate efficacy and safety of different oral doses of BAY 94-8862 given once daily over 90 days<br>;Secondary Objective: The secondary objectives are: <br>- To assess the effects of these doses on a composite endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic heart failure until Visit 9 (Day 90±2)<br>- To assess the effects of these doses on BNP, and NT-proBNP at Visit 5 (Day 30±2), Visit 7 (Day 60±2), and Visit 9 (Day 90±2)<br>- To assess the change in health-related quality of life from baseline to Visit 5 (Day 30±2) and Visit 9 (Day 90±2) assessed by the Kansas City Cardiomyopathy Questionnaire and EQ-5D-3L<br>;Primary end point(s): Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from baseline to Visit 9 (Day 90±2);Timepoint(s) of evaluation of this end point: Day 90

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. To assess the effects of these doses on a composite endpoint of death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic heart failure (WCHF) <br>2. To assess the effects of these doses on B-type natriuretic peptide (BNP), and NT-proBNP<br>3. To assess the change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire and EuroQol Group 5 dimension, 3 level questionnaire<br>;Timepoint(s) of evaluation of this end point: 1. Until V9 (Day 90)<br>2. Visit 5 (Day 30), Visit 7 (Day 60), and Visit 9 (Day 90)<br>3. From baseline to Visit 5 (Day 30) and Visit 9 (Day 90)

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