E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with decompensated chronic congested heart failure |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064653 |
E.1.2 | Term | Acute decompensated heart failure |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective of the study is to investigate the safety and efficacy of a titration phase (8 hours) and a maintenance phase (maximum 40 hours) of intravenous BAY 58-2667 in patients with decompensated chronic congestive heart failure with the need for parenteral pharmacotherapy and invasive haemodynamic monitoring (i.e. indwelling Swan-Ganz pulmonary artery catheter) and PCWP ≥ 18mmHg. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The following inclusion criteria must be met:
• Patients with decompensated chronic congestive heart failure, NYHA functional class III-IV, either ischemic or non-ischemic, requiring hospitalization, and with clinical indication for parenteral pharmacotherapy and invasive hemodynamic monitoring (i.e indwelling Swan-Ganz pulmonary artery catheter) and PCWP ≥ 18 mmgHg.
• Patients must have the clinical diagnosis of CHF made at least 3 month prior to enrollment.
• Male or female patients, age 18 years or more.
• Patients must experience worsening of at least one of the symptoms below leading to hospitalization at the time of entry into the study: Dyspnea Symptoms such as: 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). or Clinical evidence of volume overload such as: peripheral edema, hepatic congestion with ascites, pulmonary congestion/rales, or pleural effusion (chest X-ray) jugular venous distension.
• Left ventricular ejection fraction < 40 % within the last 6 months.
• History of heart failure hospitalization or IV diuretic treatment required within the last12 months.
• Ability to understand and willing to sign informed consent form.
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E.4 | Principal exclusion criteria |
The following factors determined during the run-in period will automatically exclude the subject from participating in the trial: • Females of child-bearing potential. • 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, e.g. acute myocarditis. • Unstable angina requiring angiography • Cardiogenic shock • Patients requiring any of the following: nitroprusside, intravenous nitroglycerin, nesiritide, levosimendan, any intravenous positive inotropic drug within the last 3 hours (dobutamine up to 4 µg/kg/minute is allowed). • Need for endotracheal intubation and mechanical ventilation. • Patients with cardiac arrest or patients with history of cardiac arrest within 3 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. • Patients with increased risk of cardiac arrest (e.g. QTc > 450 msec, atrial ventricular block II or III, etc.). • Ventricular fibrillation within 30 days (> 15 seconds long) • Patients showing during ECG monitoring uncontrolled ventricular rhythm disorder. • Uncontrolled atrial fibrillation or flutter or any supraventricular tachycardia. • 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). • Systolic blood pressure < 100 mmHg or > 180 mmHg. • Pulmonary embolism within the last 30 days prior to enrollment. • PDE 5 inhibitor use within the last 48 hours. • Strong CYP2C8 (inhibitors like gemfibrozil(stop at least 24 hours before study drug infusion) • Heart failure secondary to pulmonary disease and patients 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. • Known significant liver disease (e.g. acute clinical hepatitis, chronic active hepatitis, cirrhosis). • Calculated creatinine clearance < 30 mL/min. using MDRD or Cockroft Gault equation • BMI < 20 kg/m2 (BMI equal to 20 is accepted) • Drug- or alcohol abuse. • Concomitant participation in another trial or study. • Therapy with another investigational product within 30 days prior start of study • Any other condition or therapy, which in the opinion of the Principal Investigator would make the patient unsuitable for this study and presumably will not allow participation for the full planned study period.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome measure will be the change of pulmonary capillary wedge pressure (PCWP) from baseline to 8 hours versus placebo. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |