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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

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

Treatments: Drug: Levosimendan; Drug: PLACEBO

Study type: Interventional

Funder types: Other

Identifiers

NCT05233202

APHP200072

Details and patient eligibility

About

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.

Full description

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

Enrollment: 230 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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230 participants in 2 patient groups, including a placebo group

LEVOSIMEDAN

Experimental group

Description:

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.

Treatment:

Drug: Levosimendan

PLACEBO

Placebo Comparator group

Description:

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.

Treatment:

Drug: PLACEBO