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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-513811-29-00 | EU Trial (CTIS) Number |
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Cardiogenic shock (CS) mortality remains high (40%). Despite their frequent use, few clinical outcome data are available to guide the initial selection of vasoactive drug therapies in patients with CS. Based on experts' opinions, the combination of norepinephrine-dobutamine is generally recommended as a first line strategy. Inotropic agents increase myocardial contractility, thereby increasing cardiac output. Dobutamine is commonly recommended to be the inotropic agent of choice and levosimendan is generally used following dobutamine failure. It may represent an ideal agent in cardiogenic shock, since it improves myocardial contractility without increasing cAMP or calcium concentration. At present, there are no convincing data to support a specific inotropic agent in patients with cardiogenic shock. Our hypothesis is that the early use of levosimendan, by enabling the discontinuation of dobutamine, would accelerate the resolution of signs of low cardiac output and facilitate myocardial recovery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Levosimendan | Experimental | Experimental group: patients with cardiogenic shock treated with levosimendan in addition to the conventional strategy. |
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| Placebo | Placebo Comparator | Control group: Patients with cardiogenic shock treated with placebo (Cernevit/Soluvit) in addition to the conventional strategy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Levosimendan 2.5 MG/ML Injectable Solution | Drug | Levosimendan will be diluted with Glucose G5%. The reconstitution of levosimendan will be performed, as close as possible to the start of the infusion. A continuous infusion of levosimendan will be administered over 24 h without bolus, started at a rate of 0.1 μg per kilogram of body weight per minute and, in both the persistence of hypoperfusion signs and in the absence of rate-limiting side effects, will be increased after 2 to 4 hours to a maximum of 0.2 μg per kilogram per minute for a further 20 to 22 hours. |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of All-cause mortality | Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis) | Day 30 following randomization |
| Proportion of Extra Corporel Life Support implantation | Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis) | Day 30 following randomization |
| Proportion of Dialysis | Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis) | Day 30 following randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Time to death | Prioritized composite endpoint with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure). | Day 90 |
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Inclusion Criteria:
Adult patient ≥ 18 years with cardiogenic shock defined by:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bruno LEVY, Pr | Contact | +33 3 83 15 40 84 | b.levy@chru-nancy.fr |
| Name | Affiliation | Role |
|---|---|---|
| Clément DELMAS, Dr | University Hospital, Toulouse | Study Chair |
| Nicolas GIRERD, Pr | CHRU Nancy | Study Chair |
| Patrick ROSSIGNOL, Pr |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU Strasbourg -Nouvel Hôpital Civil | Recruiting | Strasbourg | Bas-Rhin | 67091 | France |
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The LevoHeartShock trial is a prospective, double-blind, multicenter, randomized controlled trial comparing the early initiation of levosimendan versus placebo in patients with cardiogenic shock treated with vasopressor therapy according to a conventional strategy of inotrope use (dobutamine as first line agent).
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The study will be double-blinded. Investigator masking to group assignment after randomization will be guaranteed by use of a placebo.
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| Placebo | Drug | Placebo will be diluted with Glucose G5%. The reconstitution of Placebo will be performed, as close as possible to the start of the infusion. A continuous infusion of Placebo will be administered over 24 h without bolus, started at a rate of 0.1 μg per kilogram of body weight per minute and, in both the persistence of hypoperfusion signs and in the absence of rate-limiting side effects, will be increased after 2 to 4 hours to a maximum of 0.2 μg per kilogram per minute for a further 20 to 22 hours. |
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| Time to escalation to permanent left ventricular assist device or cardiac transplantation | Prioritized composite endpoint with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure). | Day 90 |
| Time to dialysis | Prioritized composite endpoint with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure). | Day 90 |
| Time to ECLS requirement | Prioritized composite endpoint with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure). | Day 90 |
| number of cardiovascular events | Prioritized composite endpoint with the following priority order: 1/ time to death, 2/ escalation to permanent left ventricular assist device or cardiac transplantation, 3/ dialysis, 4/ ECLS requirement, 5/ number of cardiovascular events (stroke, recurrent myocardial infarction, urgent coronary revascularization, re-hospitalization for heart failure). | Day 90 |
| Proportion of death. | Day 90 |
| Proportion of Extra Corporel Life Support implantation | Day 90 |
| Proportion of dialysis | Day 90 |
| Proportion of cardiac transplantation | Day 90 |
| Proportion of escalation to permanent Left Ventricular Assist Device | Day 90 |
| Proportion of stroke | Day 90 |
| Proportion of recurrent myocardial infarction | Day 90 |
| Proportion of urgent coronary revascularization | Day 90 |
| Proportion of re-hospitalization for heart failure | Day 90 |
| Proportion of All-cause mortality | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90. | Day 90 |
| Proportion of Extra Corporel Life Support implantation | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90. | Day 90 |
| Proportion of Dialysis | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90. | Day 90 |
| Number of dobutamine free days | From randomization to day 30 |
| Number of vasopressors free days | From randomization to day 30 |
| Number of ventilatory free days | From randomization to day 30 |
| Number of renal replacement free days | From randomization to day 90 |
| Lactate clearance | from randomization to day 7 |
| Duration of intensive care unit stay | Up to Intensive Care Unit discharge (assessed up to 1 month) |
| Duration of hospitalization | Up to hospitalization discharge (assessed up to 1 month) |
| Proportion of All-cause mortality | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis | days 7, 60, and 180 days and 12 months |
| Proportion of Extra Corporel Life Support implantation | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis | days 7, 60, and 180 days and 12 months |
| Proportion of dialysis | Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis | days 7, 60, and 180 days and 12 months |
| Number of renal replacement free days | D 30, 60, 180 and at 12 months |
| Proportion of death | days 180 and at 12 months |
| Proportion of Extra Corporel Life Support implantation | days 180 and at 12 months |
| Proportion of dialysis | days 180 and at 12 months |
| proportion of cardiac transplantation | days 180 and at 12 months |
| proportion of escalation to permanent left ventricular assist device | days 180 and at 12 months |
| Proportion of stroke | days 180 and at 12 months |
| Proportion of recurrent myocardial infarction | days 180 and at 12 months |
| Proportion urgent coronary revascularization | days 180 and at 12 months |
| proportion of re-hospitalization for heart failure | days 180 and at 12 months |
| Occurrence of arrhythmias requiring therapy | Occurrence of arrhythmias requiring therapy with anti-arrhythmic drugs or electric cardioversion (including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, torsade de pointe) | from randomization to intensive care unit discharge. |
| the changes in biomarkers | From a dedicated biological collection on which we will measure existing and future biological parameters, we will evaluate the effect of Levosimendan on the changes in biomarkers between randomization and ICU/CCU discharge | from randomization to intensive care unit discharge. |
| All-cause mortality and/or ECLS and/or dialysis | From a dedicated biological collection on which we will measure existing and future biological parameters, we will evaluate the ability of clinical and biological measure to predict levosimendan effect for the primary endpoint. | Day 30 |
| All-cause mortality and/or ECLS and/or dialysis | From a dedicated biological collection on which we will measure existing and future biological parameters, we will evaluate the ability of biological measure to predict subsequent outcome | At intensive care unit discharge |
| CHRU Nancy |
| Study Chair |
| AP-HM, Nord Hospital, Marseille | Recruiting | Marseille | Bouches du Rhône | 13015 | France |
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| CHU Caen | Not yet recruiting | Caen | Calvados | 14000 | France |
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| CHU Dijon | Recruiting | Dijon | Côte d'Or | 21000 | France |
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| CHU Besançon Jean Minjoz Hospital | Recruiting | Besançon | Doubs | 25000 | France |
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| CHU Nîmes, Carémeau Hospital | Recruiting | Nîmes | Gard | 30029 | France |
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| CHU Bordeaux - Hopital haut-leveque | Recruiting | Bordeaux | Gironde | 33600 | France |
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| CHU de Toulouse | Recruiting | Toulouse | Haute-Garonne | 31059 | France |
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| CHU Limoges, Dupuytren Hospital | Recruiting | Limoges | Haute-Vienne | 87000 | France |
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| CHU Montpellier, Arnaud de Villeneuve Hospital | Recruiting | Montpellier | Hérault | 34090 | France |
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| CHU Rennes, Pontchaillou Hospital | Recruiting | Rennes | Ille et Vilaine | 35000 | France |
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| CHU Grenoble, Michallon Hospital | Recruiting | La Tronche | Isère | 38043 | France |
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| CHU Nantes | Recruiting | Nantes | Loire-Atlantique | 44000 | France |
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| CHR Metz-Thionville, Mercy Hospital | Recruiting | Ars-Laquenexy | Moselle | 57245 | France |
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| CHRU Lille, Cœur Poumon Institute | Recruiting | Lille | Nord | 59000 | France |
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| APHP, La Pitié Salpêtrière (medical intensive care unit) | Recruiting | Paris | Paris | 75013 | France |
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| Hospices Civils de Lyon - Louis Pradel Hospital | Recruiting | Bron | Rhône | 69500 | France |
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| APHP, Henri Mondor Hospital | Recruiting | Créteil | Val de Marne | 94010 | France |
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| CH Henri Duffaut, Avignon | Not yet recruiting | Avignon | Vaucluse | 84000 | France |
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| CHU Bordeaux | Recruiting | Bordeaux | France |
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| HENRI MONDOR -réanimation | Not yet recruiting | Créteil | France |
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| Chu Dijon | Recruiting | Dijon | France |
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| CHU Grenoble -USIC | Recruiting | La Tronche | 38700 | France |
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| AP-HM CHU la Timone | Recruiting | Marseille | 13385 | France |
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| CHU Montpellier -hôpital Arnaud de Villeneuve | Recruiting | Montpellier | 34295 | France |
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| Chu Rouen | Recruiting | Rouen | France |
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| HU Strasbourg USIC | Not yet recruiting | Strasbourg | France |
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| CHRU Nancy | Recruiting | Vandœuvre-lès-Nancy | France |
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| ID | Term |
|---|---|
| D012770 | Shock, Cardiogenic |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D000077464 | Simendan |
| ID | Term |
|---|---|
| D006835 | Hydrazones |
| D006834 | Hydrazines |
| D009930 | Organic Chemicals |
| D011724 | Pyridazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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