Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of levosimendan infusion, in addition to standard therapy,on renal function in patients with Acute Heart Failure,compared with standard therapy alone.

Detailed Description
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The term cardiorenal syndrome has been applied to the presence or development of a renal dysfunction in HF patients and may be the major precipitant of decompensation and cause for admission in these patients. The renal hypoperfusion that occurs with cardiac injury can lead to sodium and water retention and activation of the renin-angiotensin-aldosterone system and neurohormonal pathways with resultant deleterious effects on the myocardium. A vicious cycle may then ensue and be associated with increased cardiovascular complications. In this regard, renal dysfunction is of a functional nature and thus means to intervene with this vicious cycle need to be sought. Several studies already demonstrated the deleterious effects of renal dysfunction on prognosis in patients with HF due to chronic left ventricular dysfunction. Levosimendan increases myocardial contractility without significant changes in the intracellular calcium ion and cyclic adenosine monophosphate concentrations and does not enhance myocardial oxygen demand. By its action on the potassium channels this drug also dilates the coronary and peripheral arteries and exerts an anti-ischemic,anti-stunning effect. To date, the effects of levosimendan on renal function in patients with worsening chronic HF, remain unknown.

Official Title
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Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure

Conditions
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Heart Failure, Renal Insufficiency

Intervention / Treatment
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* Drug: Levosimendan in addition to standard therapy
* Drug: spironolactone, beta-blockers,ecc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: an ejection fraction (EF) 40% by transthoracic echocardiogram, a baseline pulmonary capillary wedge pressure (PCWP) 20 mm Hg a MDRD (Modification of Diet Renal Disease) score > 30 and < 60 and a standard therapy for HF that should include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, aldosterone blocking agents (spironolactone) and beta-blockers, unless contraindicated Exclusion Criteria: patients receiving other oral or i.v. inotropes, oral or i.v. diuretics or receiving nitroglycerine or nitroprusside, patients with systolic blood pressure <110 mmHg, mechanical ventilation, anticipated survival <30 days, absence of thoracic windows for echocardiography, acute coronary syndromes, sustained ventricular tachycardia or ventricular fibrillation, documented renal artery stenosis, requiring dialysis, requiring admission primarily for concurrent morbidity, severe aortic or mitral regurgitation, left ventricular failure primarily from uncorrected obstructive valvular disease, hypertrophic obstructive cardiomyopathy, restrictive/obstructive cardiomyopathy, uncorrected thyroid disease, known amyloid cardiomyopathy or known malfunctioning artificial heart valve.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>patients with acute heart failure | Drug: Levosimendan in addition to standard therapy<br>* intravenous infusion of levosimendan (10 minutes bolus with 6 mcg/Kg according to physician judgement, followed by 0.1 mcg/Kg/min for 24 hours) in addition to standard therapy<br>|
| Active Comparator: 2<br>standard therapy for heart failure | Drug: spironolactone, beta-blockers,ecc<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint: GFR measured by inulin Clearance. |  | 0, 24. 48 and 72 hours after Levosimendan infusion starting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints: •Other renal function measures: BUN, albumin, urine volume, sodium excretion and plasma sodium, and cystatin. •Hemodynamic parameters: PCWP, PAP, cardiac output, HR, BP, renal blood flow. |  | 0,1,24,48 and 72 hours after Levosimendan infusion started | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiorenal syndrome