Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01318460
• Other study ID #: AHEPA_CTS-03
• Status: Completed
• Phase: Phase 4
• Start date: March 2011
• Est. completion date: March 2014

Study information

• Verified date: May 2019
• Source: AHEPA University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Levosimendan infusion
Prophylactic 24h infusion of levosimendan at a dose of 0.1 mg/kg/min
• Placebo infusion
Twenty-four hour administration of placebo

Locations

Country	Name	City	State
Greece	Department of Cardiothoracic Surgery, AHEPA University Hospital	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
AHEPA University Hospital	Orion Corporation, Orion Pharma

Country where clinical trial is conducted

Greece, 

References & Publications (3)

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. Erratum in: Anesth Analg. 2007 Jun;104(6):1544. Dosage error in article text. — View Citation

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. — View Citation

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. Epub 2007 Aug 15. Erratum in: Eur J Cardiothorac Surg. 2008 Mar;33(3):521. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular function	Left ventricular function as assessed by transthoracic or transesophageal echocardiography on the seventh postoperative day	Seventh postoperative day
Secondary	Perioperative mortality		30 days postoperatively
Secondary	Need for intraaortic balloon pump		1st-7th postoperative day
Secondary	Inotropic support	Need for high inotropic support	1st-7th postoperative day
Secondary	Total ICU stay		1st-7th postoperative day
Secondary	Total length of hospital stay		1st-7th postoperative day
Secondary	Time on mechanical ventilation		1st-7th postoperative day
Secondary	Major adverse cardiovascular events	Perioperative myocardial infarction, stroke, need for revascularization)	1st-7th postoperative day
Secondary	Morbidity		1st-7th postoperative day