Effect of Early Use of Levosimendan Versus Placebo on Top of a Conventional Strategy of Inotrope Use on a Combined Morbidity-mortality Endpoint in Patients With Cardiogenic Shock
LevoHeartShock
1 other identifier
interventional
610
1 country
28
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2023
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2019
CompletedFirst Posted
Study publicly available on registry
July 16, 2019
CompletedStudy Start
First participant enrolled
July 3, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 3, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 3, 2028
August 5, 2025
July 1, 2025
3.6 years
June 28, 2019
July 31, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
Secondary Outcomes (41)
Time to death
Day 90
Time to escalation to permanent left ventricular assist device or cardiac transplantation
Day 90
Time to dialysis
Day 90
Time to ECLS requirement
Day 90
number of cardiovascular events
Day 90
- +36 more secondary outcomes
Study Arms (2)
Levosimendan
EXPERIMENTALExperimental group: patients with cardiogenic shock treated with levosimendan in addition to the conventional strategy.
Placebo
PLACEBO COMPARATORControl group: Patients with cardiogenic shock treated with placebo (Cernevit/Soluvit) in addition to the conventional strategy.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- Adult patient ≥ 18 years with cardiogenic shock defined by:
- Adequate intravascular volume
You may not qualify if:
- Myocardial sideration after cardiac arrest of non-cardiac etiology
- Immediate or anticipated (within 6 hours) indication of Extra Corporel Life Support
- Use of VA-ECMO or IMPELLA or LVAD;
- Chronic renal failure requiring hemodialysis
- Cardiotoxic poisoning
- Septic cardiomyopathy
- Previous levosimendan administration within 15 days
- Cardiac arrest with non-shockable rhythm;
- No flow time higher \> 3 minutes;
- Cardiac arrest with unknown no flow duration;
- Total duration of cardiac arrest (no flow plus low flow) \> 45 minutes;
- Cerebral deficit with fixed dilated pupils
- Patient moribund on the day of enrollment
- Irreversible neurological pathology
- Known hypersensitivity to levosimendan or placebo, or one of its excipients
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pr Bruno LEVYlead
Study Sites (28)
CHRU Strasbourg -Nouvel Hôpital Civil
Strasbourg, Bas-Rhin, 67091, France
AP-HM, Nord Hospital, Marseille
Marseille, Bouches du Rhône, 13015, France
CHU Caen
Caen, Calvados, 14000, France
CHU Dijon
Dijon, Côte d'Or, 21000, France
CHU Besançon Jean Minjoz Hospital
Besançon, Doubs, 25000, France
CHU Nîmes, Carémeau Hospital
Nîmes, Gard, 30029, France
CHU Bordeaux - Hopital haut-leveque
Bordeaux, Gironde, 33600, France
CHU de Toulouse
Toulouse, Haute-Garonne, 31059, France
CHU Limoges, Dupuytren Hospital
Limoges, Haute-Vienne, 87000, France
CHU Montpellier, Arnaud de Villeneuve Hospital
Montpellier, Hérault, 34090, France
CHU Rennes, Pontchaillou Hospital
Rennes, Ille et Vilaine, 35000, France
CHU Grenoble, Michallon Hospital
La Tronche, Isère, 38043, France
CHU Nantes
Nantes, Loire-Atlantique, 44000, France
CHR Metz-Thionville, Mercy Hospital
Ars-Laquenexy, Moselle, 57245, France
CHRU Lille, Cœur Poumon Institute
Lille, Nord, 59000, France
APHP, La Pitié Salpêtrière (medical intensive care unit)
Paris, Paris, 75013, France
Hospices Civils de Lyon - Louis Pradel Hospital
Bron, Rhône, 69500, France
APHP, Henri Mondor Hospital
Créteil, Val de Marne, 94010, France
CH Henri Duffaut, Avignon
Avignon, Vaucluse, 84000, France
CHU Bordeaux
Bordeaux, France
HENRI MONDOR -réanimation
Créteil, France
Chu Dijon
Dijon, France
CHU Grenoble -USIC
La Tronche, 38700, France
AP-HM CHU la Timone
Marseille, 13385, France
CHU Montpellier -hôpital Arnaud de Villeneuve
Montpellier, 34295, France
Chu Rouen
Rouen, France
HU Strasbourg USIC
Strasbourg, France
CHRU Nancy
Vandœuvre-lès-Nancy, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Clément DELMAS, Dr
University Hospital, Toulouse
- STUDY CHAIR
Nicolas GIRERD, Pr
CHRU Nancy
- STUDY CHAIR
Patrick ROSSIGNOL, Pr
CHRU Nancy
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- The study will be double-blinded. Investigator masking to group assignment after randomization will be guaranteed by use of a placebo.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Investigator coordonnator
Study Record Dates
First Submitted
June 28, 2019
First Posted
July 16, 2019
Study Start
July 3, 2023
Primary Completion (Estimated)
February 3, 2027
Study Completion (Estimated)
January 3, 2028
Last Updated
August 5, 2025
Record last verified: 2025-07