Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery

Right Heart Failure Clinical Trial

Official title:

Perioperative Use of Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05063370
• Other study ID #: FMASU R 139/2021
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 18, 2021
• Est. completion date: January 1, 2022

Study information

• Verified date: September 2021
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: January 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Open-heart Surgery
• Right Heart Failure

Intervention

Drug:
• Levosimendan
Patients will receive Levosimendan infusion 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).
• Standard Care
Patients will not receive Levosimendan and will receive standard care according to the institution protocol

Locations

Country	Name	City	State
Egypt	Cardiothoracic Academy, Ain Shams University Hospitals	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Alam M, Hedman A, Nordlander R, Samad B. Right ventricular function before and after an uncomplicated coronary artery bypass graft as assessed by pulsed wave Doppler tissue imaging of the tricuspid annulus. Am Heart J. 2003 Sep;146(3):520-6. — View Citation

Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):47G-58G. Review. — View Citation

Bootsma IT, de Lange F, Koopmans M, Haenen J, Boonstra PW, Symersky T, Boerma EC. Right Ventricular Function After Cardiac Surgery Is a Strong Independent Predictor for Long-Term Mortality. J Cardiothorac Vasc Anesth. 2017 Oct;31(5):1656-1662. doi: 10.105 — View Citation

du Toit EF, Genis A, Opie LH, Pollesello P, Lochner A. A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart. Br J Pharmacol. 2008 May;154(1):41-50. doi: 10.1038/bjp.2008.52. — View Citation

Eriksson O, Pollesello P, Haikala H. Effect of levosimendan on balance between ATP production and consumption in isolated perfused guinea-pig heart before ischemia or after reperfusion. J Cardiovasc Pharmacol. 2004 Sep;44(3):316-21. — View Citation

Haddad F, Denault AY, Couture P, Cartier R, Pellerin M, Levesque S, Lambert J, Tardif JC. Right ventricular myocardial performance index predicts perioperative mortality or circulatory failure in high-risk valvular surgery. J Am Soc Echocardiogr. 2007 Sep — View Citation

Leprán I, Pollesello P, Vajda S, Varró A, Papp JG. Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model. J Cardiovasc Pharmacol. 2006 Oct;48(4):148-52. — View Citation

Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology. 2014 May;120(5):1098-108. doi: 10.1097/ALN — View Citation

Papp Z, Édes I, Fruhwald S, De Hert SG, Salmenperä M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikström BG, Jörgensen K, Filippatos G, Parissis JT, González MJ, Parkhomenko A, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Right ventricular function	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.	7days
Primary	Right ventricular systolic pressure (RVSP)	Measured in mmhg intraoperatively by trans-esophageal echocardiography (TEE) on day 1, 3 and 7 postoperatively by transthoracic echocardiography .	7 days
Secondary	Duration of mechanical ventilation	During ICU Stay in Hours	2 Days
Secondary	Vasoactive-Inotrope score (VIS)	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.	2 Days
Secondary	Occurrence of arrhythmias	Present or no and type of arrhythmias During Hospital Stay	7 to 10 Days
Secondary	length of ICU stay	In Days	7 to 10 Days
Secondary	Length of Hospital Stay	In Days	14 Days