Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Levosimendan infusion; Drug: Placebo infusion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 546 36
    • Department of Cardiothoracic Surgery, AHEPA University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AHEPA University Hospital
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Kyriakos Anastasiadis, MD, FETCS, Ahepa University Hospital; Study Chair: Christos Papakonstantinou, MD, Ahepa University Hospital

Publications and helpful links

General Publications

• Tasouli A, Papadopoulos K, Antoniou T, Kriaras I, Stavridis G, Degiannis D, Geroulanos S. Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Eur J Cardiothorac Surg. 2007 Oct;32(4):629-33. doi: 10.1016/j.ejcts.2007.07.010. Epub 2007 Aug 15. Erratum In: Eur J Cardiothorac Surg. 2008 Mar;33(3):521.
• De Hert SG, Lorsomradee S, Cromheecke S, Van der Linden PJ. The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth Analg. 2007 Apr;104(4):766-73. doi: 10.1213/01.ane.0000256863.92050.d3. Erratum In: Anesth Analg. 2007 Jun;104(6):1544. Dosage error in article text.
• Kolseth SM, Nordhaug DO, Stenseth R, Sellevold O, Kirkeby-Garstad I, Wahba A. Prophylactic treatment with levosimendan: a retrospective matched-control study of patients with reduced left ventricular function. Eur J Cardiothorac Surg. 2009 Dec;36(6):1024-30. doi: 10.1016/j.ejcts.2009.05.001. Epub 2009 Jul 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (Estimate): March 18, 2011

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: May 4, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: cardiac surgery; coronary artery disease; levosimendan; coronary artery bypass grafting
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: AHEPA_CTS-03