Clinical trial NCT01318460: Prophylactic Administration of Levosimendan in Patients Undergoing Coronary Surgery
Official title: Prophylactic Administration of Levosimendan in Patients With Impaired Left Ventricular Function Undergoing Coronary Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: coronary artery disease
levosimendan
coronary artery bypass grafting
cardiac surgery
Lead sponsor: AHEPA University Hospital
Sponsor class: OTHER
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2011-03-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Left ventricular function
timeFrame: Seventh postoperative day
Secondary outcomes:
measure: Perioperative mortality
timeFrame: 30 days postoperatively
measure: Need for intraaortic balloon pump
timeFrame: 1st-7th postoperative day
measure: Inotropic support
timeFrame: 1st-7th postoperative day
measure: Total ICU stay
timeFrame: 1st-7th postoperative day
measure: Total length of hospital stay
timeFrame: 1st-7th postoperative day
measure: Time on mechanical ventilation
timeFrame: 1st-7th postoperative day
measure: Major adverse cardiovascular events
timeFrame: 1st-7th postoperative day
measure: Morbidity
timeFrame: 1st-7th postoperative day
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: Department of Cardiothoracic Surgery, AHEPA University Hospital
Study officials:
affiliation: AHEPA University Hospital
name: Kyriakos Anastasiadis, MD, FETCS
role: PRINCIPAL_INVESTIGATOR
affiliation: AHEPA University Hospital
name: Christos Papakonstantinou, MD
role: STUDY_CHAIR
References:
citation: 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.
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. doi: 10.1016/j.ejcts.2007.07.010. Epub 2007 Aug 15.
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.