A Placebo Controlled, Randomized, Double-Blind, Fixed-dose, Multicenter, Phase IIb Study to Investigate the Efficacy and Tolerability of BAY 58-2667 (50 µg/h, 100 µg/h, 150 µg/h) Given Intravenously to Subjects with Acute Decompensated Chronic Congestive Heart Failure (ADHF) within 12 hours after hospital admission (Pulmonary Artery Catheter eg, Swan-Ganz not required. - COMPOSE EARLY

• Conditions: Acute Decompensated Chronic Congestive Heart Failure (ADHF); MedDRA version: 12.1Level: LLTClassification code 10064653Term: Acute decompensated heart failure

• Registration Number: EUCTR2009-017082-39-IT
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-18
• Last Update Posted: 14 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Able to commence treatment within 12 hours of hospital admission (including emergency department) Subjects with ADHF, NYHA functional class III-IV requiring hospitalization Subjects must have the clinical diagnosis of CHF, either ischemic or non-ischemic, made at least three months prior to enrollment and a history of heart failure hospitalization or IV diuretic treatment required within the last 12 months Treatment with IV diuretic (after hospital admission) Subjects must experience worsening of both of the symptoms listed below leading to hospitalization admission up to study run-in. Worsening of these symptoms does not need to be displayed at baseline. o Dyspnea symptoms Dyspnea (labored or difficult breathing) at rest Dyspnea (labored or difficult breathing) on minimal exertion Orthopnea (difficult breathing except in the upright position) Nocturnal dyspnea (awaken from sleep due to respiratory distress) And o Clinical evidence of volume overload: Peripheral edema Hepatic congestion with ascites Rales or pulmonary congestion (confirmed by chest X-ray) Jugular venous distension Left ventricular ejection fraction < 40 % within the last 12 months Systolic blood pressure at inclusion of the study ≥ 120 mmHg and ≤ 180 mmHg Heart rate < 100 beats per minute Ability to understand and willing to sign informed consent form (subject or legal representative) Subject is capable of self-assessing his/her well being by applied scales after Instruction Women without childbearing potential defined as postmenopausal women aged 55 years or older, women with bilateral tubal ligation, women with bilateral ovarectomy, and women with hysterectomy or Males and non-pregnant, non-lactating females, 18 years of age or older. For females of child-bearing potential, one of the following medically acceptable contraceptive methods must be used or they agree to abstain from heterosexual intercourse while participating in the study. One or more of these methods should be used during the study and continue for 30 days after completion of the study: a) Double-barrier methods of contraception (eg, condoms plus spermicidal foam) b) Intrauterine contraceptive device c) Approved pharmaceutical contraceptive product (eg, birth control pills or patches, long-term injectable or implantable hormonal contraceptive).
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Acute de-novo heart failure Acute myocardial infarction and/or myocardial infarction within 30 days Valvular heart disease requiring surgical intervention during the course of the study Heart failure due to or associated with uncorrected primary valvular disease, malfunctioning artificial heart valve, or uncorrected congenital heart disease Primary hypertrophic cardiomyopathy Acute inflammatory heart disease, eg, acute myocarditis Unstable angina requiring angiography Cardiogenic shock Subjects requiring any of the following medication: any vasodilating drug (eg, nitrates, sodium nitroprusside), any intravenous positive inotropic drug (eg, levosimendan, dobutamine), or any natriuretic petide (eg, nesiritide, carperitide) within the last three hours prior to dosing with study medication Need for endotracheal intubation and mechanical ventilation Subjects with cardiac arrest or subjects with history of cardiac arrest within three months, unless precipitated by an event such as an acute myocardial infarction, induction by catheter placement, severe transient electrolyte abnormality, an electrophysiology procedure, or addressed by automatic implantable cardioverter defibrillator placement Subjects with increased risk of cardiac arrest (eg, QTc > 450 msec, atrial ventricular block II or III) Sustained ventricular tachycardia within 30 days (duration > 15 seconds) Subjects showing during ECG monitoring sustained or unsustained ventricular tachycardia, either monomorphic or polymorphic (unless precipitated by an event such as catheter placement) Uncontrolled atrial fibrillation or flutter or any supraventricular tachycardia with a ventricular rate more than 110 bpm for more than 30 minutes Cardiac surgery within the last month (such as cardiac revascularization surgery, valvular surgery, biventricular resynchronization procedure, ventricular reduction surgery or cardiac myoplasty, implantation of mechanical ventricular assist device) Pulmonary embolism within the last 30 days prior to enrollment PDE 3 inhibitor use within the last 48 hours prior to onset of study drug infusion Strong CYP2C8 inhibitors like gemfibrozil (stop at least 24 hours before study drug infusion) Heart failure secondary to pulmonary disease and subjects with primary pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension History of or clinically significant evidence of any severe disease other than heart failure that preclude participation Clinical relevant hepatic dysfunction (eg, induced by acute clinical hepatitis, chronic active hepatitis, cirrhosis) indicated by: - bilirubin > 2 times upper limit normal - and/or hepatic transaminases > 3 times upper limit normal - and/or signs of severe hepatic insufficiency (eg, impaired albumin synthesis with albumin < 35g/l, hepatic encephalopathy > Stage 1 (according to West Haven Criteria of Altered Mental Status In Hepatic Encephalopathy: Stage 0: Lack of detectable personality changes. No asterixis; Stage 1: Trivial lack of awareness. Impaired attention span. Altered sleep, euphoria or depression. Mild asterixis may be present; Stage 2: Lethargy or apathy. Disorientation. Inappropriate behavior. Slurred speech. Asterixis; Stage 3: Gross disorientation. Bizarre behavior. Semi-stupor. Asterixis absent; Stage 4: Coma) Calculated creatinine clearance < 30 mL/min. using MDRD (Modification of Diet Renal Disease) Body mass index (BMI) < 20 kg/m2 (BMI equal to 2

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified