Levosimendan Versus Dobutamine for Renal Function in Heart Failure

Study Overview
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Brief Summary
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Although inotropes have a favorable effect on central hemodynamics in patients with heart failure, their effect on renal hemodynamics is incompletely defined. The purpose of this study is to evaluate the efficacy of a 75 min intravenous infusion of levosimendan compared to a 75 min infusion of dobutamine on renal hemodynamics and function in patients with chronic heart failure and signs of cardiorenal syndrome. The investigators hypothesis is that patients treated with levosimendan will show greater increases in renal blood flow and glomerular filtration rate (GFR) than those treated with dobutamine.

Official Title
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Efficacy of Intravenous Levosimendan Compared With Dobutamine on Renal Hemodynamics and Function in Chronic Heart Failure

Conditions
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Cardiorenal Syndrome

Intervention / Treatment
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* Drug: Levosimendan
* Drug: Dobutamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, signed and dated informed consent Male and Female subjects ≥18 years of age Chronic congestive heart failure scheduled for right sided cardiac catheterization Left ventricular ejection fraction ≤ 40% determined by echocardiography Elevation of N Terminal-proBNP ≥ 500 ng/L Cardiorenal syndrome (30ml/min ≤ estimated GFR ≤ 80 ml/min (MDRD) Exclusion Criteria: Acute heart failure, untreated Systolic blood pressure < 80 mmHg Tachycardia above 100 bpm Angina Canadian Cardiovascular Society (CCS) class III or higher Aortic stenosis Hypertrophic cardiomyopathy Restrictive cardiomyopathy The presence of kidney disease diagnosed before heart failure Administration of radiographic contrast < 1 week Radiographic contrast allergy In the Investigator's opinion, the patient has a clinically significant disease that could be adversely affected by study participation

Ages Eligible for Study
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Minimum Age: 18 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levosimendan<br>Levosimendan administration is initiated with a loading dose of 12μg/kg given over 10 min followed by a continuous infusion of 0.1 μg/kg/min for 65 min. | Drug: Levosimendan<br> <br> * Other names: Simdax;|
| Active Comparator: Dobutamine<br>Dobutamine is given as a continuous infusion without a bolus dose. The infusion rate is started at 5.0 μg/kg/min for 10 minutes, and thereafter increased to 7,5 μg/kg/min for 65 min. | Drug: Dobutamine<br> <br> * Other names: Dobutrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in renal blood flow | Para-aminohippuric acid (PAH) infusion clearance | 75 min minus baseline | 
| Change in glomerular filtration rate | Chrome-ethylenediaminetetraacetic acid (EDTA) infusion clearance | 75 min minus baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in renal vascular resistance | Renal blood flow divided by the difference between renal arterial pressure and renal venous pressure | 75 min minus baseline | 
| Change in central hemodynamics | Right atrial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, mean arterial pressure, cardiac output, pulmonary vascular resistance and systemic vascular resistance measured with a pulmonary artery thermodilution catheter. | 75 min minus baseline | 
| Change in renal oxygen consumption and oxygen extraction | Oxygen consumption: Renal blood flow multiplied by arterial-renal venous oxygen difference. Oxygen extraction: Ratio of renal oxygen consumption to renal oxygen delivery | 75 min minus baseline | 
| Change in filtration fraction | Ratio of glomerular filtration rate to renal plasma flow | 75 min minus baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Renal failure, Inotropic drugs, Levosimendan, Dobutamine