Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

Study Overview
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Brief Summary
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The present pilot study aims to investigate the effectiveness of the preoperative infusion of levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting.

Detailed Description
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Myocardial revascularization in patients with impaired left ventricular function remains a serious problem in cardiac surgery. Despite the recent developments with the use of new surgical techniques (mini-extracorporeal circulation, off pump surgery) the perioperative morbidity and mortality are relatively high. Therapeutic solutions with the use of inotropic drugs, as adrenergic agonists and phosphodiesterase inhibitors, have offered important improvement to the hemodynamic status of these patients, but they have not considerably decreased mortality. These drugs owe their positive inotropic action to the increase of intracellular calcium and thereafter they improve the myocardial function. Levosimendan (SIMDAX) is a new calcium sensitizer which increases the myocardial contractility without particular promotion of the intracellular calcium accumulation. Contemporary experimental and clinical data demonstrated the effectiveness of this drug in the reduction of surgical mortality to the patients with low left ventricular ejection fraction (LVEF) who undergo coronary artery bypass grafting (CABG). This is an original prospective randomized controlled study focused on the preoperative use of this drug in patients with impaired left ventricular function which is associated with a high operative risk (i.e. EuroSCORE). Perioperative myocardial stunning is particularly evident in this cohort of patients. Prophylactic administration of levosimendan the day before the operation could be translated in improved myocardial performance intraoperatively and during the early postoperative period.

Official Title
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Prophylactic Administration of Levosimendan in Patients With Impaired Left Ventricular Function Undergoing Coronary Surgery

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Levosimendan infusion
* Drug: Placebo infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: coronary artery disease which warrants myocardial revascularization with coronary artery bypass grafting according to current guidelines age < 79 years old left ventricular ejection fraction <= 40% informed patient's consent Exclusion Criteria: age < 18 years old emergency surgery medical history of acute myocardial infarction with ST elevation (STEMI) less than 14 days old any severe comorbidity which increases the perioperative risk (i.e. neoplasia, rheumatoid arthritis, chronic obstructive pulmonary disease) need for valvular replacement surgery redo surgery serum creatinine > 2 mg/dl history of malignant cardiac arrhythmias

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levosimendan<br>Patients treated with prophylactic administration of levosimendan | Drug: Levosimendan infusion<br>* Prophylactic 24h infusion of levosimendan at a dose of 0.1 mg/kg/min<br>|
| Placebo Comparator: Placebo group<br>Patients managed with placebo administration | Drug: Placebo infusion<br>* Twenty-four hour administration of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function | Left ventricular function as assessed by transthoracic or transesophageal echocardiography on the seventh postoperative day | Seventh postoperative day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative mortality |  | 30 days postoperatively | 
| Need for intraaortic balloon pump |  | 1st-7th postoperative day | 
| Inotropic support | Need for high inotropic support | 1st-7th postoperative day | 
| Total ICU stay |  | 1st-7th postoperative day | 
| Total length of hospital stay |  | 1st-7th postoperative day | 
| Time on mechanical ventilation |  | 1st-7th postoperative day | 
| Major adverse cardiovascular events | Perioperative myocardial infarction, stroke, need for revascularization) | 1st-7th postoperative day | 
| Morbidity |  | 1st-7th postoperative day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, levosimendan, coronary artery bypass grafting, cardiac surgery