Clinical trial NCT05063370: Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery
Official title: Perioperative Use of Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery With Cardiopulmonary Bypass
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Right Heart Failure
Open-heart Surgery
Keywords: levosimendan
TAPSE
Heart Failure
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2021-10-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Right ventricular function
timeFrame: 7days
measure: Right ventricular systolic pressure (RVSP)
timeFrame: 7 days
Secondary outcomes:
measure: Duration of mechanical ventilation
timeFrame: 2 Days
measure: Vasoactive-Inotrope score (VIS)
timeFrame: 2 Days
measure: Occurrence of arrhythmias
timeFrame: 7 to 10 Days
measure: length of ICU stay
timeFrame: 7 to 10 Days
measure: Length of Hospital Stay
timeFrame: 14 Days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cardiothoracic Academy, Ain Shams University Hospitals
Study officials:
References:
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