The Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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A study to evaluate the effectiveness and safety of levosimendan compared with placebo in subjects with severe aortic stenosis and heart failure undergoing transcatheter aortic valve replacement

Detailed Description
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The number of subjects undergoing transcatheter aortic valve replacement to treat aortic stenosis have been increasing in recent decades. Levosimendan, an innovative inotrope, is powerfully evidenced to have the function to improve cardiac output and hemodynamic parameters. However, there is no specified study concentrated on the role of Levosimendan in surgical procedure such as transcathter aortic intervention. This double-blind, randomized, placebo-controlled study is aimed to investigate the effectiveness and safety of Levosimendan in adults having severe aortic stenosis combined with heart failure undergoing transcatheter aortic valve replacement. Therefore, the purpose of this trial is to explore whether the improvement of cardiac and renal performance can be rendered by intra-operative Levosimendan infusion.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement

Conditions
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Inotropic Agents, Safety Issues, Effect of Drug, Cardiac Event, Transcatheter Aortic Valve Replacement, Aortic Valve Stenosis, Heart Failure

Intervention / Treatment
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* Drug: Levosimendan
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed (by the subjects or their legally acceptable representatives) informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Severe aortic stenosis Mean transaortic gradient ≥ 40 mmHg(at rest or stress) Aortic peak velocity ≥ 4m/s; Arotic valve area <0.8 cm2 and/or aortic valve area index< 0.5cm2/m2 Cardiac dysfunction LVEF≤50% (estimated by Simpson) NT-proBNP≥1500ng/L； Symptoms of dyspnea and fatigue when at rest or after slight exertion (New York Heart Association ≥ Ⅲ -Ⅳ) Intermittant fluid retention and/or symptoms induced by low cardiac output at rest, but lack of hemodynamic instability Exclusion Criteria: Decompensated acute cardiac failure due to hemodynamic instability A historty of torsade de points ventricular tachycardia Known allergic reaction or sensitivity to Levosimendan or excipients Received levosimendan within 1 week prior to the planned clinical trial Serum potassium < 3.5 mmol/L and > 5.5 mmol/L before the drug study Systolic blood pressure < 90mmHg at baseline Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2. Unable to participate in study for being critically ill asssed by clinicians Other concomitant severe morbidities leading to poor prognosis and decreased mortality, such as malignant tumor and disease involving other vital organs; life expectancy less than 1 year.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levosimendan<br>Levosimendan 0.1µg/kg/min will last for 24h after the valve is released. | Drug: Levosimendan<br>* On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min levosimendan is given for 24 hours.<br>|
| Placebo Comparator: Placebo<br>5% glucose 0.1µg/kg/min administration will continue for 24h after the valve is released. | Other: Placebo<br>* On the basis of routine care given by corresponding clinicians, 0.1µg/kg/min 5% glucose infusion is given for 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of NT-proBNP level |  | day 1, day 3, day 5, month 1 and month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of CK-MB |  | day 1, day 3, day 5, month 1 and month 3 | 
| The change of c-TnI |  | day 1, day 3, day 5, month 1 and month 3 | 
| The change of left ventricular ejection fraction | It is evaluated by echcardiography. | day 1, day 3, day 5, month 1 and month 3 | 
| The change of left ventricular end-diastolic diameter | It is evaluated by echcardiography. | day 1, day 3, day 5, month 1 and month 3 | 
| The number of patients in need of secondary intra-operative vasoactive-inotropic substances | Vasoactive-inotropic substances include dobutamine, milrinone, epinephrine, dopamine and vasopressors. | Peri-operation | 
| The incidence of postoperative kidney injury | The kidney injury will be assessed by the change of serum creatinine, urea nitrogen and cystatin C. | day 1, day 3, day 5, month 1 and month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve stenosis, Heart failure, Levosimendan, Transcatheter Aortic Valve Replacement, Effectiveness, Safety, NT-proBNP