Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.

Efficacy and Safety of Short-term Intravenous Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients Treated With Beta-receptor Blocking Agents.

The purpose of this study is to compare the effects of levosimendan with dobutamine on heart function in patients suffering of severe chronic heart failure.

Patients with decompensate heart failure (NYHA III-IV) and in need of intravenous inotrop support and who fulfil all inclusion and no exclusion criteria will be randomised into the study in proportion 1:1. Although stratification will be done so patients treated with beta-receptor blocker carvedilol will be divided the same between the study groups.

All patients will receive infusions in parallell, one of the groups will receive active product (levosimendan or dobutamine) and the other will receive placebo (double-dummy technique).

Catheterisation for measurement of hemodynamic parameters will be performed according to routine methods at the clinic. The measurements of the hemodynamic variables will start 30 minutes before start of study drug infusion and will be finished 48 hours after start of infusion. The most important variables during the measurements is Cardiac Index (CI)and Pulmonary Capillary Wedge Pressure (PCWP).

Parallel registration will be done on ECG, blood pressure, blood frequency, central venous pressure, and lung artery pressure. Heart failure and other clinical symptoms will be registered continuously during 48 hours. Blood samples will be taken intermittent to record the blood values. Cogent rules for decreasing/increasing of the dose can be found in the study protocol, likewise rules for interruption or stoop for infusion.

Registration of side-effects will be done continuously. The recommendation for treatment for known side effects could be found in the protocol (section 5.3.4) and the protocol should be available during the study procedure.

One month after the study the patients will be followed up with a very careful examination and also of the amount of visits and reason for visits to hospital during the past 30-35 days.

Main Inclusion Criteria:

• Decompensated chronic heart failure of ischemic or non-ischemic origin, in NYHA class III to IV, despite optimised conventional treatment and who may benefit from intravenous positive inotropic agents as per the investigator's judgment.
• Ongoing treatment with a beta-receptor blocking agent in a stable regimen for at least 3 months and at an optimal dose as per the investigator's judgment.
• Left ventricular (LV) ejection fraction (EF) less than or similar to 35%.
• CI < 2.5 l/min/m2.
• Mean PCWP >15 mmHg.

Main Exclusion Criteria:

• Significant mechanical obstruction affecting ventricular filling and/or outflow.
• Systolic blood pressure 85 mmHg or less at screening and/or baseline.
• Heart rate 130 bpm or greater, persistent for at least 5 minutes at screening and/or baseline.
• Severe angina pectoris during the 6 hours before screening and/or baseline.
• Deterioration of chronic heart failure due to an acute myocardial infarction within 5 days before screening measurements.
• Administration of Simdax within 1 month before baseline.
• A history of Torsades de Pointes.
• Evidence of severe renal insufficiency (serum creatinine > 450 μmol/l or on dialysis) at screening.
• Significant hepatic impairment or elevation of liver enzymes to 5 times the upper limit of normal range of the analysing laboratory at screening.
• Acute bleeding or severe anaemia.
• Heart surgery within 3 months before baseline.