A Phase 4 interventional study of Levosimendan and Placebo in Heart Failure, sponsored by Centro Cardiologico Monzino. Completed at 1 site in Italy. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2015-11-06.
Sponsored by Centro Cardiologico Monzino · Phase 4, Interventional, and Treatment
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.
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
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 42 is below the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Centro Cardiologico Monzino is the lead sponsor of 69 studies on the registry; 24 are open to participants now.
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Exclusion Criteria:
Levosimendan must be diluted before the administration (500 ml of glucose). The intravenous infusion may be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. 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. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response.
Drug: Levosimendan
Placebo must be diluted before the administration (500 ml of glucose). The intravenous infusion may' be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. 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. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response.
Drug: 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.
Also known as: SIMDAX
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.
Change in Peak VO2 (Oxygen Consumption )
Primary endpoints: Levosimendan induced changes in peak VO2 (Oxygen consumption )
Time frame: 48 hours
Changes in VE/VCO2
Levosimendan induced changes on VE/VCO2 (VE: Expired Volume - VCO2: carbon dioxide production) relationship
Time frame: 48 hours
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.
Time frame: 48 hours
From September 2012 to December 2014 we enrolled forty-two patients who fulfilled the study inclusion/ exclusion criteria:19 patients received placebo and 23 received levosimendan. All patients was enrolled at Centro Cardiologico Monzino.
| Milestone | Levosimendan | Placebo |
|---|---|---|
| Started | 23 | 19 |
| Completed | 23 | 19 |
| Not completed | 0 | 0 |
Primary endpoints: Levosimendan induced changes in peak VO2 (Oxygen consumption )
| ml/kg/min | Levosimendan | Placebo |
|---|---|---|
| Change in Peak VO2 (Oxygen Consumption ) | 1.21 ± 1.9 | 0.48 ± 1.2 |
Levosimendan induced changes on VE/VCO2 (VE: Expired Volume - VCO2: carbon dioxide production) relationship
| VE/VCO2 Slope | Levosimendan | Placebo |
|---|---|---|
| Changes in VE/VCO2 | -5.34 ± 7 | -0.91 ± 4.7 |
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.
| ml/mmHg/min | Levosimendan | Placebo |
|---|---|---|
| Change in DLCO (Diffusion Lung CO) | -0.96 ± 2 | 0.88 ± 3.14 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Levosimendan | — | 0/23 (0%) | 0/23 (0%) |
| Placebo | — | 0/19 (0%) | 0/19 (0%) |
| Age, Categorical(Participants) | Levosimendan | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 4 | 10 |
| >=65 years | 17 | 15 | 32 |
| Age, Continuous(years) | Levosimendan | Placebo | Total |
|---|---|---|---|
| Mean | 70.39 ± 9.4 | 68.2 ± 8.3 | 69 ± 8.7 |
| Sex: Female, Male(Participants) | Levosimendan | Placebo | Total |
|---|---|---|---|
| Female | 4 | 3 | 7 |
| Male | 19 | 16 | 35 |
| Region of Enrollment(participants) | Levosimendan | Placebo | Total |
|---|---|---|---|
| Italy | 23 | 19 | 42 |
| NYHA class(units on a scale) | Levosimendan | Placebo | Total |
|---|---|---|---|
| Mean | 3.3 ± 0.4 | 3.2 ± 0.4 | 3.3 ± 0.47 |
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Centro Cardiologico Monzino