Adult patients with acute cardiogenic shock refractory to conventional therapy placed on VA-ECMO support and for whom withdrawal from ECMO is possible. MedDRA version: 20.0 Level: PT Classification code 10007625 Term: Cardiogenic shock System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: ZIMINO 12.5 mg (levosimendan) 2,5 mg/ml
Product Name: ZIMINO 12.5 mg (levosimendan) 2,5 mg/ml
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for in
Sponsors
ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Acute cardiogenic shock patient refractory to conventional therapy placed on VA-ECMO support in the preceding 48h. 2. Obtain informed consent from a close relative or surrogate. According to the urgent inclusion procedure, randomization may take place and the consent of a close relative or surrogate will be sought as soon as possible. The patient's consent to prosecute will be sought as soon as his condition permits. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 103 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 103
Exclusion criteria
Exclusion criteria: 1. Age 48 h 4. Resuscitation >30 minutes before ECMO 5. Irreversible neurological pathology 6. End-stage cardiomyopathy with no hope of LV function recovery 7. Mechanical complication of myocardial infarction 8. Aortic regurgitation > II 9. VA-ECMO for pulmonary embolism 10. VA-ECMO for cardiotoxic drug intoxication 11. VA-ECMO after left-ventricle assist device implantation 12. VA-ECMO in heart transplant patients 13. Patient moribund on the day of randomization, SAPS II >90 14. Liver cirrhosis (Child B or C) and other severe hepatic insufficiency 15. Chronic renal failure requiring hemodialysis 16. Known hypersensitivity to levosimendan 17. Prior history of “torsades de pointes” 18. History of epilepsy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of early administration of Levosimendan on the time to successful ECMO weaning (defined below) within the 30 days following randomization, in patients with VA-ECMO support for acute cardiogenic shock refractory to conventional therapy.;Secondary Objective: - Mortality on D30 and D60 - Duration of ECMO support between inclusion-D30, and between inclusion-D60; and number of ECMO-free days between inclusion and D30-D60 -Duration of ICU stay-hospitalization - Major adverse cardiovascular events on days 30 and 60 - Time to improvement in hemodynamics and time to hemodynamic stabilization - Number of days with organ failure, defined by SOFA score, and number of days without organ failure between inclusion and D30 - Duration of hemodynamic support with catecholamines and number of days alive without hemodynamic support between inclusion and D30 - Duration of mechanical ventilation and number of days alive without mechanical ventilation between inclusion and D30 and D60 - LV function assessed with echocardiography at Day 30 following randomization - Incidence of drug adverse effects - Primary and secondary endpoints in predefined subgroups: acute myocardial infarction, myocarditis, post-cardiac surgery and post-cardiac arrest patients.;Primary end point(s): Time to successful ECMO weaning within the 30 days following randomization. : -ECMO weaning will be considered successful only if the patient survives without ECMO, other mechanical circulatory support device or heart transplantation 30 days after ECMO removal. -Thus all ECMO weaning from randomization to 30 days after randomization will be considered, and the qualification for successful ECMO weaning will need 30 days of follow-up after ECMO removal (thus until day 60 after randomization for an ECMO weaning performed on day 30 after randomization). -Patients still under ECMO 30 days after randomization will be considered as censored. -The number of days alive without ECMO was not | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Mortality on Day 30 and Day 60 - Total duration of ECMO support between inclusion and D30 and between inclusion andD60; - Number of ECMO-free days between inclusion and D30/D60. - Duration of ICU stay and of hospitalization; - Major adverse cardiovascular events defined as death, cardiac transplant, escalation to permanent left ventricular assist device, stroke, dialysis, re-hospitalization for heart failure on days 30 and 60 - Time to improvement in hemodynamic parameters (systolic, diastolic, mean blood pressure, heart rate …) and time to hemodynamic stabilization - Days with organ failure, defined by the SOFA score, and days alive without organ failure between inclusion and D30; - Duration of hemodynamic support with catecholamines and days alive without hemodynamic support between inclusion and D30; - Duration of mechanical ventilation and days alive without mechanical ventilation between inclusion and D30 and D60; - LV function assessed with echocardiography at Day 30 following randomization - Incidence of adverse drug reactions (including atrial fibrillation and other supraventricular arrhythmias, ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes, hypokalemia). - Primary and secondary endpoints in predefined subgroups: acute myocardial infarction, myocarditis, post-cardiac surgery and post-cardiac arrest patients. ;Timepoint(s) of evaluation of this end point: Day 0 to Day 60 | — |
Countries
France
Contacts
Public ContactPôle Promotion-DRCI
ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (AP-HP)
Outcome results
None listed