Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery

October 12, 2021 updated by: Ain Shams University

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11566
        • Cardiothoracic Academy, Ain Shams University Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Levosimendan group
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).
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).
OTHER: Standard group
Patients will not receive Levosimendan perioperatively and will be managed with standard care according to our institutional protocol
Drug: Standard Care
Patients will not receive Levosimendan and will receive standard care according to the institution protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Right ventricular function
Time Frame: 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.
7days
Right ventricular systolic pressure (RVSP)
Time Frame: 7 days
Measured in mmhg intraoperatively by trans-esophageal echocardiography (TEE) on day 1, 3 and 7 postoperatively by transthoracic echocardiography .
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of mechanical ventilation
Time Frame: 2 Days
During ICU Stay in Hours
2 Days
Vasoactive-Inotrope score (VIS)
Time Frame: 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.
2 Days
Occurrence of arrhythmias
Time Frame: 7 to 10 Days
Present or no and type of arrhythmias During Hospital Stay
7 to 10 Days
length of ICU stay
Time Frame: 7 to 10 Days
In Days
7 to 10 Days
Length of Hospital Stay
Time Frame: 14 Days
In Days
14 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 18, 2021

Primary Completion (ANTICIPATED)

December 1, 2021

Study Completion (ANTICIPATED)

January 1, 2022

Study Registration Dates

First Submitted

September 10, 2021

First Submitted That Met QC Criteria

September 21, 2021

First Posted (ACTUAL)

October 1, 2021

Study Record Updates

Last Update Posted (ACTUAL)

October 20, 2021

Last Update Submitted That Met QC Criteria

October 12, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMASU R 139/2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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