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

NCT ID: NCT04020263

Last Updated: 2025-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

610 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-03

Study Completion Date

2028-01-03

Brief Summary

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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.

Detailed Description

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Conditions

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Cardiogenic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
The study will be double-blinded. Investigator masking to group assignment after randomization will be guaranteed by use of a placebo.

Study Groups

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Levosimendan

Experimental group: patients with cardiogenic shock treated with levosimendan in addition to the conventional strategy.

Group Type EXPERIMENTAL

Levosimendan 2.5 MG/ML Injectable Solution

Intervention Type 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.

Placebo

Control group: Patients with cardiogenic shock treated with placebo (Cernevit/Soluvit) in addition to the conventional strategy.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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Levosimendan 2.5 MG/ML Injectable Solution

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Adult patient ≥ 18 years with cardiogenic shock defined by:

* Adequate intravascular volume
* Norepinephrine to maintain MAP at least at 65 mmHg for at least 3 hours and less than 24h. At inclusion the dose must be \<1 microgram/kg/min under norepinephrine base or \<2 microgram/kg/min under norepinephrine tartrate, OR/AND Dobutamine since at least 3h and less than 24h at inclusion.
* Tissue hypoperfusion: at least 1 sign within 24h prior to inclusion (lactate ≥ 2 mmol/l; mottling, capillary refeel time \> 3 seconds, oliguria \<500ml/24h or ≤ 20 ml/h during the last 2 hours, ScVO2 ≤ 60% or veno-arterial PCO2 gap ≥ 5 mmHg);

Exclusion Criteria

* 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
* Pregnant woman, birthing or breastfeeding mother
* Minor (not emancipated)
* Person deprived of liberty for judicial or administrative decision;
* Adult subject to a legal protection measure (such as guardianship, conservatorship)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pr Bruno LEVY

OTHER

Sponsor Role lead

Responsible Party

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Pr Bruno LEVY

Investigator coordonnator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Clément DELMAS, Dr

Role: STUDY_CHAIR

University Hospital, Toulouse

Nicolas GIRERD, Pr

Role: STUDY_CHAIR

CHRU Nancy

Patrick ROSSIGNOL, Pr

Role: STUDY_CHAIR

CHRU Nancy

Locations

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CHRU Strasbourg -Nouvel Hôpital Civil

Strasbourg, Bas-Rhin, France

Site Status RECRUITING

AP-HM, Nord Hospital, Marseille

Marseille, Bouches du Rhône, France

Site Status RECRUITING

CHU Caen

Caen, Calvados, France

Site Status NOT_YET_RECRUITING

CHU Dijon

Dijon, Côte d'Or, France

Site Status RECRUITING

CHU Besançon Jean Minjoz Hospital

Besançon, Doubs, France

Site Status RECRUITING

CHU Nîmes, Carémeau Hospital

Nîmes, Gard, France

Site Status RECRUITING

CHU Bordeaux - Hopital haut-leveque

Bordeaux, Gironde, France

Site Status RECRUITING

CHU de Toulouse

Toulouse, Haute-Garonne, France

Site Status RECRUITING

CHU Limoges, Dupuytren Hospital

Limoges, Haute-Vienne, France

Site Status RECRUITING

CHU Montpellier, Arnaud de Villeneuve Hospital

Montpellier, Hérault, France

Site Status RECRUITING

CHU Rennes, Pontchaillou Hospital

Rennes, Ille et Vilaine, France

Site Status RECRUITING

CHU Grenoble, Michallon Hospital

La Tronche, Isère, France

Site Status RECRUITING

CHU Nantes

Nantes, Loire-Atlantique, France

Site Status RECRUITING

CHR Metz-Thionville, Mercy Hospital

Ars-Laquenexy, Moselle, France

Site Status RECRUITING

CHRU Lille, Cœur Poumon Institute

Lille, Nord, France

Site Status RECRUITING

APHP, La Pitié Salpêtrière (medical intensive care unit)

Paris, Paris, France

Site Status RECRUITING

Hospices Civils de Lyon - Louis Pradel Hospital

Bron, Rhône, France

Site Status RECRUITING

APHP, Henri Mondor Hospital

Créteil, Val de Marne, France

Site Status RECRUITING

CH Henri Duffaut, Avignon

Avignon, Vaucluse, France

Site Status NOT_YET_RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

HENRI MONDOR -réanimation

Créteil, , France

Site Status NOT_YET_RECRUITING

Chu Dijon

Dijon, , France

Site Status RECRUITING

CHU Grenoble -USIC

La Tronche, , France

Site Status RECRUITING

AP-HM CHU la Timone

Marseille, , France

Site Status RECRUITING

CHU Montpellier -hôpital Arnaud de Villeneuve

Montpellier, , France

Site Status RECRUITING

Chu Rouen

Rouen, , France

Site Status RECRUITING

HU Strasbourg USIC

Strasbourg, , France

Site Status NOT_YET_RECRUITING

CHRU Nancy

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Bruno LEVY, Pr

Role: CONTACT

+33 3 83 15 40 84

Facility Contacts

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Ferhat MEZIANI, MD-PhD

Role: primary

Laurent Bonello, MD

Role: primary

Katrien Blanchart, MD

Role: primary

Jean-Pierre Quenot, MD-PhD

Role: primary

Hadrien WINISZEWSKI, MD

Role: primary

Benoît Lattuca, MD

Role: primary

Edouard Gerbaud, MD

Role: primary

Clément Delmas, MD

Role: primary

Philippe Vignon, MD

Role: primary

François Roubille, MD

Role: primary

Abdelkader BAKHTI, MD

Role: primary

Joanna Bougnaud, MD

Role: primary

Julien Plessis, MD

Role: primary

Guillaume Louis, MD

Role: primary

Gilles LEMESLE, MD-PhD

Role: primary

Alain Combes, MD

Role: primary

Bertrand SCHEPPLER, MD

Role: primary

+33 4 72 11 80 88

Raphaëlle HUGUET, MD

Role: primary

+33 1 49 81 21 11

Stéphane Andrieu, MD

Role: primary

Alexandre OUTARRA, MD-PhD

Role: primary

Armand MEKONTSO DESSAP, MD-Phd

Role: primary

+33 1 49 81 21 11

Pierre Grégoire GUINOT, MD-PhD

Role: primary

Nicolas PILIERO, MD

Role: primary

Florent ARREGLE, MD

Role: primary

Philippe GAUDARD, MD-PhD

Role: primary

Emmanuel BESNIER, MD-PhD

Role: primary

Olivier MOREL, MD PhD

Role: primary

+33 3 88 11 67 68

Bruno Lévy, Prof

Role: primary

Other Identifiers

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2024-513811-29-00

Identifier Type: CTIS

Identifier Source: secondary_id

2024-513811-29-00

Identifier Type: -

Identifier Source: org_study_id

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