Patients Referred for an Isolated or a Combined Surgical Correction of Functional Moderate to Severe Tricuspid
Conditions
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
Interventions
DRUGLevosimendan
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.
DRUGPLACEBO
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.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Prospective, multicenter, randomized (two arms, parallel groups); double-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the effects of CTAC on ventilation/perfusion ratios during a moderate to severe ARDS | day 90 | 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
| Measure | Time frame | Description |
|---|---|---|
| incidence of Refractory Hypotension (Drug safety) | day 90 | the study drug safety is defined as a refractory hypotension. |
| Number of catecholamine infusion | during 90 days | persistence of infusion beyond 48 hours after cardiac surgery |
| Number of circulatory mechanical assist devices | during 90 days | the need of circulatory mechanical assist devices in the postoperative period |
| Number of renal replacement therapy | during 90 days | Need for renal replacement therapy at any time during intensive care unit stay |
Countries
France
Contacts
Primary ContactPascal LIM, MD, PhD
Backup ContactAkim SOUAG
Outcome results
None listed