Clinical trial NCT01969071: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Mitral Valve Stenosis With Incompetence or Regurgitation
Keywords: levosimendan
mitral valve surgery
cardiopulmonary bypass
serum creatinine
estimated glomerular filtration rate
ejection fraction
Lead sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2013-10-25
Enrollment: 140
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
timeFrame: 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 outcomes:
measure: The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery.
timeFrame: 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 outcomes:
measure: The effects of levosimendan on renal function in patients with low ejection fraction undergoing mitral valve surgery
timeFrame: 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.
Locations:
city: Istanbul
country: Turkey
facility: Kartal Kosuyolu High Speciality Training and Research Hospital
Study officials:
affiliation: Kartal Kosuyolu High Speciality Training and Research H
name: Ayse Baysal, MD
role: PRINCIPAL_INVESTIGATOR
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