E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
Patients referred for an isolated or a combined surgical correction of functional moderate to severe tricuspid regurgitation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068176 |
E.1.2 | Term | Coronary artery bypass graft |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
The secondary end points were 1) each component of the primary end point, and 2) the study drug safety defined as refractory hypotension. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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)
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is a composite element reflecting low cardiac output syndrome: - 1) Catecholamine infusion persisting beyond 48 hours after cardiac surgery, - 2) Need for circulatory mechanical assist devices in the postoperative period, - 3) 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 primary end-point is defined as event occurring during the post-operative hospitalization period in intensive care unit. This period is usually limited at 90 days.
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E.5.2 | Secondary end point(s) |
The secondary end points were: - Mortality at day 90, - Each component of the primary end point, - The study drug safety was assessed by recording of the incidence refractory hypotension was defined as a failure to increase mean arterial pressure above 60 mmHg despite optimal management.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 18 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |