Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction (LEONARD)
Primary Purpose
Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Levosimendan
PLACEBO
Sponsored by
About this trial
This is an interventional treatment trial for Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid
Eligibility Criteria
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
Sites / Locations
- Assistance Publique Hôpitaux de Paris-Hôpital Henri MondorRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LEVOSIMEDAN
PLACEBO
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
incidence of Refractory Hypotension (Drug safety)
the study drug safety is defined as a refractory hypotension.
Number of catecholamine infusion
persistence of infusion beyond 48 hours after cardiac surgery
Number of circulatory mechanical assist devices
the need of circulatory mechanical assist devices in the postoperative period
Number of renal replacement therapy
Need for renal replacement therapy at any time during intensive care unit stay
Full Information
NCT ID
NCT05233202
First Posted
February 9, 2022
Last Updated
May 11, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT05233202
Brief Title
Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction
Acronym
LEONARD
Official Title
Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 23, 2023 (Actual)
Primary Completion Date
January 23, 2025 (Anticipated)
Study Completion Date
January 23, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, multicenter, randomized (two arms, parallel groups); double-blind, placebo-controlled study
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
230 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
LEVOSIMEDAN
Arm Type
Experimental
Arm 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.
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Levosimendan
Other Intervention Name(s)
Experimental arm
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
PLACEBO
Other Intervention Name(s)
Control arm
Intervention 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.
Primary Outcome Measure Information:
Title
Evaluate the effects of CTAC on ventilation/perfusion ratios during a moderate to severe ARDS
Description
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.
Time Frame
day 90
Secondary Outcome Measure Information:
Title
incidence of Refractory Hypotension (Drug safety)
Description
the study drug safety is defined as a refractory hypotension.
Time Frame
day 90
Title
Number of catecholamine infusion
Description
persistence of infusion beyond 48 hours after cardiac surgery
Time Frame
during 90 days
Title
Number of circulatory mechanical assist devices
Description
the need of circulatory mechanical assist devices in the postoperative period
Time Frame
during 90 days
Title
Number of renal replacement therapy
Description
Need for renal replacement therapy at any time during intensive care unit stay
Time Frame
during 90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pascal LIM, MD, PhD
Phone
(0)1.49.81.45.84
Ext
33
Email
pascal.lim@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Akim SOUAG
Phone
(0)1 44 84 17 15
Ext
33
Email
akim.souag@aphp.fr
Facility Information:
Facility Name
Assistance Publique Hôpitaux de Paris-Hôpital Henri Mondor
City
Créteil
ZIP/Postal Code
94000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pascal LIM, Pr
Phone
0033-149812111
Ext
33
Email
lim.pascal.hmn@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction
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