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The Effects of Levosimendan During Mitral Valve Surgery

Primary Purpose

Mitral Valve Stenosis With Incompetence or Regurgitation

Status
Completed
Phase
Phase 4
Locations
Turkey
Study Type
Interventional
Intervention
Levosimendan
Dobutamine
Sponsored by
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Mitral Valve Stenosis With Incompetence or Regurgitation focused on measuring levosimendan, mitral valve surgery, cardiopulmonary bypass, serum creatinine, estimated glomerular filtration rate, ejection fraction

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Kartal Kosuyolu High Speciality Training and Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Levosimendan, inotropic agent

Control

Arm Description

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.

In the control group, only standard inotropic therapy (one or more agent including; dopamine, dobutamine, noradrenaline, adrenaline)will be administered

Outcomes

Primary Outcome Measures

The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
The effects of levosimendan on postoperative renal function measured by serum creatinine (sCr) levels and estimated glomerular filtration rate (eGFR).

Secondary Outcome Measures

The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
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.

Full Information

First Posted
May 24, 2013
Last Updated
October 23, 2013
Sponsor
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01969071
Brief Title
The Effects of Levosimendan During Mitral Valve Surgery
Official Title
The Effects of Levosimendan on Renal Function in Patients With Low Ejection Fraction Undergoing Mitral Valve Surgery.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitral Valve Stenosis With Incompetence or Regurgitation
Keywords
levosimendan, mitral valve surgery, cardiopulmonary bypass, serum creatinine, estimated glomerular filtration rate, ejection fraction

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levosimendan, inotropic agent
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
In the control group, only standard inotropic therapy (one or more agent including; dopamine, dobutamine, noradrenaline, adrenaline)will be administered
Intervention Type
Drug
Intervention Name(s)
Levosimendan
Other Intervention Name(s)
Symdax
Intervention Description
The effects of levosimendan on renal function
Intervention Type
Drug
Intervention Name(s)
Dobutamine
Other Intervention Name(s)
Dobutrex
Intervention Description
Standard Inotropic agent
Primary Outcome Measure Information:
Title
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
Description
The effects of levosimendan on postoperative renal function measured by serum creatinine (sCr) levels and estimated glomerular filtration rate (eGFR).
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 Outcome Measure Information:
Title
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
Description
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.
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.
Other Pre-specified Outcome Measures:
Title
The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery
Description
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).
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayse Baysal, MD
Organizational Affiliation
Kartal Kosuyolu High Speciality Training and Research H
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kartal Kosuyolu High Speciality Training and Research Hospital
City
Istanbul
ZIP/Postal Code
34846
Country
Turkey

12. IPD Sharing Statement

Citations:
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11092663
Citation
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The Effects of Levosimendan During Mitral Valve Surgery

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