Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction

Study Overview
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Brief Summary
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A Prospective, multicenter, randomized (two arms, parallel groups); double-blind, placebo-controlled in order to assess the ability of preoperative levosimendan to prevent post-operative low cardiac output in high-risk patients referred to cardiac surgery for correcting functional tricuspid regurgitation. The primary end point is a composite element that includes peri-operative mortality and low cardiac output syndrome at day-90: 1) catecholamine infusion persisting beyond 48 hours after cardiac surgery, 2) the need for circulatory mechanical assist devices in the postoperative period, 3) or the need for renal replacement therapy at any time during intensive care unit stay. If a patient had at least 1 of these criteria, he or she was considered as meeting the primary end point.The secondary end points were 1) each component of the primary end point, and 2) the study drug safety defined as refractory hypotension.

Detailed Description
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Patients referred for an isolated or a combined surgical correction of functional moderate to severe tricuspid are randomized in 2 arms, the levosimendan group or to the placebo group. In the experimental group, levosimendan is administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin 24H to 48H before anesthetic induction. In the comparator group, Placebo (isotonic sodium) administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin <48H before anesthetic induction

Official Title
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Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction

Conditions
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Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid

Intervention / Treatment
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* Drug: Levosimendan
* Drug: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients referred for an isolated or a combined surgical correction of functional moderate to severe tricuspid regurgitation [effective regurgitant orifice (ERO)>20mm², or systolic hepatic vein flow blunting or reversal] Written signed informed consent Affiliation to the French health care system (Sécurité Sociale) Exclusion Criteria: Age < 18 years Severe organic renal dysfunction defined by creatinine clearance <30mL/min Recent endocarditis (<3 months) Recent myocardial infarction (<3 months) Tricuspid valve perforation or prolapse Cardiogenic shock requiring dobutamine support or cardiac assistance Severe liver injury (CHILD C) Left ventricular obstruction Allergy to levosimedan Current participation in other investigational drug or device studies or being in the exclusion period at the end of a previous study involving human participants, if applicable Pregnant or breastfeeding women Females of childbearing potential without effective method of birth control Patient on AME (state medical aid) unless exemption from affiliation Hypotension with SBP<90mmHg Severe tachycardia History of torsade de pointe

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multicenter, randomized (two arms, parallel groups); double-blind, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEVOSIMEDAN<br>Levosimendan administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin 24H to 48H before anesthetic induction. | Drug: Levosimendan<br>* Levosimendan administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin 24H to 48H before anesthetic induction.<br>* Other names: Experimental arm;|
| Placebo Comparator: PLACEBO<br>Placebo (isotonic sodium) administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin <48H before anesthetic induction. | Drug: PLACEBO<br>* Placebo (isotonic sodium) administered as a continuous infusion over a 24-hour period at the rate of 0.2μg/kg/min, with no bolus administration. The infusion will begin <48H before anesthetic induction.<br>* Other names: Control arm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effects of CTAC on ventilation/perfusion ratios during a moderate to severe ARDS | The primary end point is a composite element that includes peri-operative mortality and low cardiac output syndrome at day-90: 1) catecholamine infusion persisting beyond 48 hours after cardiac surgery, 2) the need for circulatory mechanical assist devices in the postoperative period, 3) or the need for renal replacement therapy at any time during intensive care unit stay. If a patient had at least 1 of these criteria, he or she was considered as meeting the primary end point. | day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of Refractory Hypotension (Drug safety) | the study drug safety is defined as a refractory hypotension. | day 90 | 
| Number of catecholamine infusion | persistence of infusion beyond 48 hours after cardiac surgery | during 90 days | 
| Number of circulatory mechanical assist devices | the need of circulatory mechanical assist devices in the postoperative period | during 90 days | 
| Number of renal replacement therapy | Need for renal replacement therapy at any time during intensive care unit stay | during 90 days |