The Effects of Levosimendan During Mitral Valve Surgery

October 23, 2013 updated by: Ayse Baysal, Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

The Effects of Levosimendan on Renal Function in Patients With Low Ejection Fraction Undergoing Mitral Valve Surgery.

The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery will be investigated in a prospective, double-blinded, randomized clinical trial using serum creatinine (sCr)milligram in deciliter (mg/dL) values, calculated estimated glomerular filtration(eGFR)(ml/min/1.73 m2) rates and perioperative clinical follow-up parameters.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction:

The coronary and peripheral vasodilatory properties of levosimendan has recently been investigated in patients with heart failure. It is considered as a promising alternative to conventional inotropic agents for patients with low LVEF. However, the effects of levosimendan on renal functions in patients undergoing open heart surgeries with CPB are not well studied in randomized clinical trials.

The primary goal of our study was to investigate the effects of levosimendan on 1- renal function by evaluation of serum creatinine (mg/dL) values and calculated estimated glomerular filtration(eGFR)(ml/min/1.73 m2) rates.

Our secondary goal was to determine clinical outcomes including;

1-need for renal replacement therapy (RRT) in patients with low ejection fraction undergoing mitral valve repair or replacement surgery with cardiopulmonary bypass (CPB).

Inclusion and exclusion criterions include as listed below. Patients included into the study had a diagnosis of mitral valve insufficiency with or without coronary artery disease and a left ventricular ejection fraction (LVEF) of ≤ 45 %.

Exclusion criteria were unstable angina, diabetes mellitus treated with insulin, clinical findings of acute or chronic renal failure (serum creatinine (sCr)> 1.5 mg/dL), severe hepatic disease (alanine aminotransferase or aspartate aminotransferase > 100 U litre/L), severe chronic obstructive pulmonary disease (forced expired volume in 1 s < 50 % of predicted or < 2.0 litre), a history of prior coronary artery bypass graft (CABG) surgery or myocardial infarction (MI) within the previous month, emergent operations, patients on inotropic support before operation, aortic valvular disease, and infective endocarditis.

The study protocol:

The patients will be randomized into two groups. Randomization into two groups was performed using sealed envelopes and the sequentially numbered assignments of the participant which will be concealed in an envelope and will be opened after anesthesia induction by a health care personnel. The observers will be blinded to the inotropic protocol. Caregivers will not be blinded, but they will not participate in data collection or data interpretation.

In the levosimendan group, a loading it of levosimendan (6 μg/kg) will be administered after removal of the aortic cross-clamp, followed by an infusion of levosimendan at a dose of 0.1 μg/kg/min in addition to standard inotropic therapy (one or more agent including; dobutamine, epinephrine or norepinephrine)for 24 hours. In the control group, only standard inotropic therapy will be administered.

The need for renal replacement therapy (RRT)will be provided to all patients under the following criterions: 1- when urine output was less than 100 mL within the last 8 hours, 2- with no response to 50 mg intravenous dose of furosemide, 3- urine sodium concentration should be > 40 milliequivalent/liter (mEq/L) before administration of furosemide, 4- blood urea nitrogen (BUN) level > 50 mg/dl 5-additional presence of one or more of the following factors such as; a- increase in serum creatinine level > 50% from preoperative value, b- presence of metabolic acidosis, c- presence of hypervolemia, d- presence of hyperkalemia (potassium ion level > 5 Meq/L).

The study parameters:

The demographic data includes; age, weight, height, body mass index and gender. The cardiovascular risk factors including; diabetes mellitus, hypertension, hypercholesterolemia, obesity, history of smoking as well as history of chronic obstructive pulmonary disease and peripheral vascular disease were sought.

Echocardiographic data were performed to evaluate the ejection fraction and valvular functions by the same cardiologist using a Vivid 3 echocardiography device (Healthcare General Electronics,Hamburg,Germany) before operation and on first hour, 12 and 24 hour after operation.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure (MPAP) >25 mmHg at rest. The diagnosis of PH depends on direct measurement of the mean PAP by right heart catheterization. However, we used Doppler echocardiographic study to provide an estimate of the pulmonary artery systolic pressure (PASP)and mean PAP is calculated with the formula: mean PAP = 0.65 PASP + 0.55 mmHg.

The risk of operation will be evaluated using the European System for the Cardiac Operation Risk Evaluation scale (EuroSCORE).

Acute kidney injury (AKI) is defined as increase in serum creatinine from baseline by > 50 % within 48 hours postoperatively.

SCr levels will be collected on preoperative and postoperative days 1, 3 and 10 and and eGFR will be calculated according to the abbreviated Modification of Diet in Renal Disease (MDRD) equation.

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 4

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

  • Turkey
      • Istanbul, Turkey, 34846
        • Kartal Kosuyolu High Speciality Training and Research Hospital

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

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • diagnosis of mitral valve insufficiency with or without coronary artery disease and a LVEF of ≤ 45 %.

Exclusion criteria:

  • unstable angina,
  • diabetes mellitus treated with insulin, clinical findings of acute or chronic renal failure (sCr > 1.5 mg dL-1),
  • severe hepatic disease (alanine aminotransferase or aspartate aminotransferase > 100 U litre L-1),
  • severe chronic obstructive pulmonary disease (forced expired volume in 1 s < 50 % of predicted or < 2.0 litre),
  • a history of prior CABG surgery or myocardial infarction (MI) within the previous month,
  • emergent operations,
  • patients on inotropic support before operation,
  • aortic valvular disease, and
  • infective endocarditis.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Levosimendan, inotropic agent
In the levosimendan group, levosimendan will be used in addition to standard inotropic therapy (one or more agent including; dopamine, dobutamine, noradrenaline, adrenaline)for 24 hours.Levosimendan dosage; a loading dose of levosimendan (6 μg kg-1) will be administered after removal of the aortic cross-clamp, followed by an infusion of levosimendan at a dose of 0.1 μg kg-1 min-1.
Drug: Levosimendan
The effects of levosimendan on renal function
Other Names:
  • Symdax
Active Comparator: Control
In the control group, only standard inotropic therapy (one or more agent including; dopamine, dobutamine, noradrenaline, adrenaline)will be administered
Drug: Dobutamine
Standard Inotropic agent
Other Names:
  • Dobutrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
Time Frame: Between the time period of July 1, 2009 to January 30, 2013 participants will be followed for the duration of hospital stay, an expected average of 10 days.
The effects of levosimendan on postoperative renal function measured by serum creatinine (sCr) levels and estimated glomerular filtration rate (eGFR).
Between the time period of July 1, 2009 to January 30, 2013 participants will be followed for the duration of hospital stay, an expected average of 10 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
Time Frame: Between the time period of July 1, 2009 to January 30, 2013 participants will be followed for the duration of hospital stay, an expected average of 10 days.
Secondary end points were the effects of levosimendan on clinical outcomes which include the pre- and perioperative prognostic risk factors such as; 1-aortic cross-clamp time, 2- cardiopulmonary bypass time, 3- the use of inotropic support, 4-intra-aortic balloon pump, 5- prolonged mechanical ventilation, 6-development of pneumonia, 7- Perioperative myocardial infarction, 8- cerebrovascular event (stroke, transient ischemic attack), 9- atrial fibrillation and other rhythm disturbances, 10- need for renal replacement therapy (RRT), 11-reoperation secondary to bleeding, 12-intensive care unit stay and 13- hospital stay.
Between the time period of July 1, 2009 to January 30, 2013 participants will be followed for the duration of hospital stay, an expected average of 10 days.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery
Time Frame: Between the time period of July 1, 2009 to January 30, 2013 all patients will be evaluated participants will be followed for the duration of hospital stay, an expected average of 10 days.

Hemodynamic measurements include;

1- Cardiac output, 2-cardiac index (CI), 3-mean arterial pressure (MAP), 4-heart rate (HR), were recorded just before the start of surgery, at the end of CPB, on admission to the ICU, and postoperatively at 6 and 24 h later in the ICU. Hemodynamic targets were as follows: MAP ≥70 mmHg, CI ≥ 2.0 L/min/m2 without signs of poor peripheral perfusion (oliguria, acidosis).
Between the time period of July 1, 2009 to January 30, 2013 all patients will be evaluated participants will be followed for the duration of hospital stay, an expected average of 10 days.

Collaborators and Investigators

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

Sponsor

Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

Investigators

  • Principal Investigator: Ayse Baysal, MD, Kartal Kosuyolu High Speciality Training and Research H

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

July 1, 2009

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

May 24, 2013

First Submitted That Met QC Criteria

October 23, 2013

First Posted (Estimate)

October 25, 2013

Study Record Updates

Last Update Posted (Estimate)

October 25, 2013

Last Update Submitted That Met QC Criteria

October 23, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • No: 2013.2/1

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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