Intracoronary Administration of Levosimendan in Cardiac Surgery Patients

Incomplete recovery from ischemia causes stunned myocardium. Ischemia may be due to coronary artery disease or aortic cross-clamping during surgery. Stunning leads to myocardial dysfunction. It has been suggested that the mechanism responsible for the contractile depression in stunned myocardium is a decreased sensitivity of the myofibrils to calcium. Levosimendan is a calcium sensitizer, which has been shown to improve the function of stunned myocardium without obvious impairment of diastolic function. Systemic vasodilation and need of vasoconstrictive medication is usually apparent after administration of levosimendan. Colucci et al have demonstrated that with intracoronary administration of milrinone, another inodilator, systemic vasodilation could be excluded. If this is true with levosimendan, it may be possible to improve left ventricular hypo/dyskinesia without afterload reduction by adding levosimendan into cardioplegia solution.

The investigators hypotize that levosimendan, delivered together with cardioplegia, can improve LV dysfunction after opening of aortic cross-clamp in patients undergoing aortic valve and coronary artery bypass operation. Our primary endpoint is a change in cardiac output 15 min after separation from cardiopulmonary bypass compared to the baseline. Secondary endpoints are a change in LV ejection fraction from baseline to 5 min after sternal closure and cTnT/CK-MB on the first postoperative morning.

Study Overview

• Status: Terminated
• Conditions: Myocardial Stunning
• Intervention / Treatment: Drug: levosimendan; Drug: Vitamin B 12

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland, 33521
    • Heart Center Co. Tampere university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• preoperative LVEF 40% or less
• septal wall thickness more than 11mm
• less than moderate aortic insufficiency
• sinus rhythm before CPB

Exclusion Criteria:

• oesophageal disease
• known allergy to levosimendan or its metabolites or adjuvants.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Vitamin B 12; Infusion made of Glucos B.Braun 50 mg/ml infusion together with vitamin B12 which is used to colour the glucose infusion to look identical to Simdax infusion The placebo will be administered together with the induction of cardioplegia solution during five minutes (=once for each patient).; Other Names: Soluvit (B05XC)
Active Comparator: levosimendan	Drug: levosimendan; infusion; levosimendan (12 μg/kg) The study drug will be administered together with the induction of cardioplegia solution during five minutes (=once for each patient); Other Names: Simdax (manufacturer: Orion Corporation); CO1CX08

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in cardiac output	Our primary endpoint is a change in cardiac output 15 min after separation from cardiopulmonary bypass compared to the baseline (after induction of anesthesia).	from baseline to 15min after weaning from CPB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EF	Secondary endpoint is a change in LV ejection fraction (EF) from baseline (after induction of anesthesia) to 5 min after sternal closure.	from baseline to 5 min after sternal closure
cTnT/CK-MB on the first postoperative morning.	Secondary endpoint is a change in cTnT/CK-MB on the first postoperative morning.	from baseline to 1st post. op. morning

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Investigators: Principal Investigator: Panu Virkkala, MD, Heart Center Co. Tampere university hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2018
• Primary Completion (Actual): December 15, 2018
• Study Completion (Actual): September 11, 2019

Study Registration Dates

• First Submitted: December 22, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (Estimate): December 28, 2011

Study Record Updates

• Last Update Posted (Actual): September 13, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Myocardial Stunning; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Vitamin B 12; Hydroxocobalamin; Simendan
• Other Study ID Numbers: HCA-2011-1-3; 2011-002643-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No