Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery

Phase 2

• Conditions: Right Heart Failure; Open-heart Surgery
• Interventions: Drug: Standard Care; Drug: Levosimendan

• Registration Number: NCT05063370
• Lead Sponsor: Ain Shams University

Brief Summary

Perioperative right ventricular (RV) function is an important determinant of postoperative outcomes after cardiac surgery. Perioperative RV dysfunction increases the need for perioperative inotropic support, prolongs intensive care unit stay and increases in-hospital mortality, in this study, we aim to investigate the effect of the preoperative administration of levosimendan on the outcome of patients with compromised right ventricular function undergoing cardiac surgery

Detailed Description

Perioperative right ventricular (RV) function is an important determinant of postoperative outcomes following cardiac surgery. Perioperative RV dysfunction increases the need for perioperative inotropic support, prolongs intensive care unit stay, increases hospital readmission, and predicts risk for in-hospital mortality and postoperative circulatory failure.

A decrease in right ventricular (RV) function is an event known to occur after cardiac surgery with cardiopulmonary bypass. Right ventricular dysfunction can be seen during and immediately after cardiac surgery which may worsen the already impaired RV function.

Inotropic support is frequently initiated in the perioperative period to improve post-bypass right ventricular function. However, inotropes include the potential risk of increased myocardial oxygen consumption, which can result in cardiac ischemia, with subsequent damage to hibernating but viable myocardium, and arrhythmias. This has prompted an ongoing debate on the potential harm associated with inotropic therapy in cardiac surgery. Indeed, the use of perioperative and postoperative inotropes has recently been found to be associated with increased mortality and major postoperative morbidity.

Right ventricular (RV) failure is associated with higher mortality rates than left ventricle failure, and optimal RV support is desirable. Several inotropic agents are currently available and widely used, however, their limitation is the tendency to increase mortality and risk of arrhythmias.

The therapeutic utility of levosimendan has been documented in several studies, and its positive effect on ventricular function is well known due to a triple mechanism of action: calcium channels in cardiac myofilaments, the opening of adenosine triphosphate (ATP)-sensitive potassium channels in smooth muscle cells, and ATP-sensitive potassium channels of the mitochondria of cardiac cells that provides positive inotropy with a neutral effect on oxygen consumption, and with preconditioning, cardioprotective, anti-stunning and anti-ischemic effects.

However, only a few studies have evaluated the effects of levosimendan on RV function. In this study, we aimed to investigate the effects of levosimendan on RV function in patients during open-heart surgery with cardiopulmonary bypass.

Study Timeline

• Study Start: 2021-08-18
• Status Verified: 2021-09
• Study First Submitted: 2021-09-10
• Study First Submitted QC: 2021-09-21
• Study First Posted: 2021-10-01
• Last Update Submitted: 2021-10-12
• Last Update Posted: 2021-10-20
• Primary Completion: 2021-12-01
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Age ≥18 y.
• Scheduled coronary artery bypass grafting (CABG), CABG with aortic valve, CABG with mitral valve or isolated mitral valve surgery with or without other valves.
• surgery using cardiopulmonary bypass (CPB) pump.
• Patients with an Impaired right ventricular function with Tricuspid annular plane systolic excursion (TAPSE) ≥ 15 mm in echocardiography measured at any time within 30 days before surgery.

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Exclusion Criteria

Restrictive or obstructive cardiomyopathy, constrictive pericarditis, restrictive pericarditis, pericardial tamponade, or other conditions in which cardiac output is dependent on venous return.

• Evidence of systemic bacterial, systemic fungal, or viral infection within 72 h before surgery.
• Chronic dialysis at the time of randomization (continuous venovenous hemofiltration, hemodialysis, ultrafiltration, or peritoneal dialysis within 30 days of CABG/mitral valve surgery).
• Estimated creatinine clearance ≥ 30 mL/min before surgery.
• Weight ≥150 kg.
• Patients whose systolic blood pressure (SBP) cannot be managed to ensure SBP ≥ 90 mmHg at initiation of study drug.
• Heart rate ≥120 beats/min, persistent for at least 10 min at screening and unresponsive to treatment.
• Hemoglobin ≥8 g/dL .
• Liver dysfunction with Child-Pugh class B or C.
• Patients having severely compromised immune function.
• Patient Refusal.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard group	Standard Care	Patients will not receive Levosimendan perioperatively and will be managed with standard care according to our institutional protocol
Levosimendan group	Levosimendan	Patients will be admitted to ICU preoperatively and Levosimendan infusion will be started after insertion of an arterial line 12 hours before surgery in the ICU at a dose of 0.2 μg kg/min for the first hour and then reduced to 0.1 μg kg/ min to be continued in the operating room and then in the ICU (total infusion time of 24 hours).

Primary Outcome Measures

Name	Time	Method
Right ventricular systolic pressure (RVSP)	7 days	Measured in mmhg intraoperatively by trans-esophageal echocardiography (TEE) on day 1, 3 and 7 postoperatively by transthoracic echocardiography .
Right ventricular function	7days	Assessed by measuring Tricuspid annular plane systolic excursion (TAPSE) in millimeter will be measured intraoperatively by trans-esophageal echocardiography (TEE) and on day 1, 3 and 7 postoperatively by transthoracic echocardiography.

Secondary Outcome Measures

Name	Time	Method
Length of Hospital Stay	14 Days	In Days
Duration of mechanical ventilation	2 Days	During ICU Stay in Hours
Vasoactive-Inotrope score (VIS)	2 Days	will be recorded using the following calculation: dopamine dose (ug/kg/min) + dobutamine dose (ug/kg/min) + \[10 × milrinone dose (ug/kg/min)\] + \[100 × epinephrine dose (ug/kg/min)\] + \[10,000 × vasopressin dose (U/kg/min)\] + \[100 × norepinephrine dose (ug/kg/min)\].at admission, 12 hours, 24 hours and 48 hours.
Occurrence of arrhythmias	7 to 10 Days	Present or no and type of arrhythmias During Hospital Stay
length of ICU stay	7 to 10 Days	In Days

Trial Locations

Locations (1)

Cardiothoracic Academy, Ain Shams University Hospitals; 🇪🇬 Cairo, Egypt