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: 16.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857; MedDRA version: 16.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861; MedDRA version: 16.1Level: LLTClassification code 10066498Term: Cardiac failure chronic aggravatedSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2012-002627-15-FI
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-20
• Last Update Posted: 6 January 2015

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 adequate contraception' is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. 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)