Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support: a Multicentre, Parallel-Group, Randomised, Double-Blind, Double-Dummy Study of Levosimendan Versus Dobutamine in Patients With Acute Heart Failure.

Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support: a Multicentre, Parallel-Group, Randomised, Double-Blind, Double-Dummy Study of Levosimendan Versus Dobutamine in Patients With Acute Heart Failure.

The primary objective of the study is to compare the efficacy of levosimendan and dobutamine on all-cause mortality in the 180 days following randomization.

Inclusion Criteria:

• Written, signed and dated informed consent

• Male and female patients over 18 years of age. Females of childbearing potential must have a negative pregnancy test and must refrain from breastfeeding. Women who are postmenopausal [two years since last menstrual cycle], surgically sterilised or who have undergone a hysterectomy are considered not to be of childbearing potential

• Hospitalised patients with acutely decompensated heart failure

• Left ventricular ejection fraction less than or equal to 30 % as assessed using echocardiography, radionuclide ventriculography or contrast angiography within 12 months

• Clinical need for intravenous inotropic support as evidenced by insufficient response to intravenous diuretics and/or vasodilators (nitroglycerin, nitroprusside) and at least one of the following at screening:

  • oliguria (mean urine output < 30 ml/h for at least 6 hours) and not a result of hypovolemia
  • dyspnoea at rest or mechanical ventilation for heart failure
  • haemodynamic impairment in those patients with Swan-Ganz catheter inserted (PCWP ≥ 18 mmHg and/or Cardiac Index ≤ 2.2 l/min/m2)

Exclusion Criteria:

• Severe obstruction of ventricular outflow tracts such as haemodynamically significant uncorrected primary valve disease or hypertrophic cardiomyopathy or impaired ventricular filling such as restrictive cardiomyopathy
• Weight ≥ 160 kg
• Cardiac surgery within 30 days before screening
• Stroke within 3 months before screening
• Systolic blood pressure persistently less than 85 mmHg at screening or at baseline
• Heart rate persistently 130 bpm or greater at screening or at baseline
• Serum potassium less than 3.5 mmol/l at screening
• Administration of any inotropic agent (e.g. dobutamine, milrinone, amrinone, enoximone, epinephrine, norepinephrine) except digitalis or dopamine (with dose of less than or equal than 2 mg/kg/min) during the current hospitalisation
• Hypersensitivity to levosimendan or dobutamine or any of their excipients
• A history of Torsades de Pointes
• Severe renal insufficiency (serum creatinine > 450 mmol/l [5.0 mg/dl]) or on dialysis
• Significant hepatic impairment at discretion of the investigator
• Acute bleeding
• Severe anemia (haemoglobin < 8 g/dl) at screening
• Septicaemia or septic shock
• Other serious diseases limiting life expectancy considerably (e.g. end-stage cancer)
• Participation in a clinical trial with any experimental treatment within 30 days prior to screening or previous participation in the present study
• Administration of levosimendan within 30 days prior to screening