Clinical trial NCT02261948: Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)
Official title: Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Keywords: Cardiac Failure
Severe Heart Failure
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2014-10-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Eligibility criteria: Inclusion Criteria:

* informed consent of the study signed
* severe heart failure in stable clinical condition (NYHA class III, peak VO2 \<12 ml / kg / min) in optimized medical therapy. The clinical stability is defined by the stability of the therapy, the weight and urine output for 3 days

Exclusion Criteria:

* unstable patients from a clinical point of view, not in optimized therapy
* patients unable to perform a CPET (Cardiopulmonary Exercise Test) .
* are excluded from the protocol also patients with absolute contraindications to CPET (acute myocardial infarction, severe aortic stenosis, myocarditis or pericarditis, active, acute thromboembolism, sepsis,unstable angina, uncontrolled arrhythmia.
* age \< 18 years.

Primary outcomes:
measure: Change in Peak VO2 (Oxygen Consumption )
timeFrame: 48 hours
Secondary outcomes:
measure: Changes in VE/VCO2
timeFrame: 48 hours
measure: Change in DLCO (Diffusion Lung CO)
timeFrame: 48 hours
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
state: MI
Study officials:
affiliation: Centro Cardiologico Monzino,IRCCS
name: Piergiuseppe Agostoni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: