Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)

Heart Failure Clinical Trial

Official title:

Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02261948
• Other study ID #: CCFM 199/312
• Status: Completed
• Phase: Phase 4
• First received: July 22, 2014
• Last updated: October 7, 2015
• Start date: September 2012
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: Centro Cardiologico Monzino
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Levosimendan
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.
• Placebo
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.

Locations

Country	Name	City	State
Italy	Centro Cardiologico Monzino	Milano	MI

Sponsors (2)

Lead Sponsor	Collaborator
Centro Cardiologico Monzino	Orion Corporation, Orion Pharma

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Peak VO2 (Oxygen Consumption )	Primary endpoints: Levosimendan induced changes in peak VO2 (Oxygen consumption )	48 hours	No
Secondary	Changes in VE/VCO2	Levosimendan induced changes on VE/VCO2 (VE: Expired Volume - VCO2: carbon dioxide production) relationship	48 hours	No
Secondary	Change in DLCO (Diffusion Lung CO)	Levosimendan induced changes on DLCO ( Diffusion Lung CO). DLCO is measured by the single breath-constant expiratory flow technique (Sensor Medics 2200, Yorba Linda, CA) and we calculate also the DLCO adjusted for hemoglobin. Dilution of CH4 is used to measure alveolar volume.	48 hours	No