Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 4

Summary: 
      The present study was conceived to evaluate the effects of levosimendan on cardiopulmonary
      exercise test (CPET) and DLCO ( Diffusion capacity of Lung for carbon monoxide) in patients
      with severe heart failure in stable clinical conditions (NYHA - New York Heart Association -
      class III, with a peak VO2 (Oxygen consumption ) < 12 ml/min/kg) on top of optimized standard
      therapy.
    

Detailed description: 
      Eligible patients should have chronic HF (Heart Failure -class NYHA III or IV) in stable
      clinical conditions. Inclusion criteria were: left ejection fraction (EF) at echocardiography
      ≤35%, age ≥18 years old, peak VO2 <12 ml/min/kg measured by a CPET, a standard optimized
      therapy for HF that include ACE-inhibitors, ARBs (angiotensin II Receptor Blocker),
      aldosterone blocking agents (spironolactone), diuretics, and beta-blockers.

      The exclusion criteria are: ongoing mechanical ventilation; recent or acute coronary
      syndromes; sustained ventricular tachycardia or ventricular fibrillation; severe aortic or
      mitral regurgitation, or known malfunctioning artificial heart valve; uncorrected obstructive
      valvular disease; hypertrophic obstructive cardiomyopathy; uncorrected thyroid disease.

      Patients will be randomly assigned by means of prepared letters to the levosimendan or
      placebo group stratified by clinical centre in a 1:1 allocation using block randomization.
      The placebo infusion will be coloured identically to its respective active counterpart.
      Patients and investigators will be kept blinded to the treatment allocation for the entire
      duration of the trial. Study drug will be infused with an injection speed between 6 and 20
      ml/min based on blood pressure, without a bolus, for 24 hours.

      Medical history, physical examination and a blood sample examination will be recorded: NYHA
      class, BNP (Brain Natriuretic Peptide), haemoglobin, creatinine, blood urea nitrogen (BUN)
      will be recorded before and 24 hours after the drug infusion.

      A two-dimensional standard echocardiography evaluation will be performed at the admission in
      the hospital.

      A maximal CPET performed on a cycle ergometer (Sensor Medics Ergo 800S and V-max,
      Yorba-Linda, CA) with a personalized ramp aimed at achieving peak exercise in 10 minutes will
      be performed before and 24 hours after the drug infusion. Expiratory O2, CO2 (Carbon dioxide)
      and ventilation (VE) will be measured breath by breath. Peak VO2 (Carbon dioxide production)
      was considered to be the highest VO2 achieved during the exercise. A 12-lead
      electrocardiogram will be also recorded. Spirometry and DLCO measurements will be performed
      before ad 24-hours after the drug infusion. . DLCO will be measured by the single
      breath-constant expiratory flow technique
    

Intervention name(s): Levosimendan; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min.; Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min.
Other intervention name(s): SIMDAX
Intervention MeSH terms: Simendan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Cardiac Failure; Severe Heart Failure