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Cardiogenic ShockPhase 3LevoHeartShockNCT04020263

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

A Phase 3 study testing Levosimendan 2.5 MG/ML Injectable Solution in people with Cardiogenic Shock, run by Pr Bruno LEVY at 28 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cardiogenic Shock
What is being tested?
Levosimendan 2.5 MG/ML Injectable Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
610 participants
Where
28 sitesFrance
Study dates
3 Jul 2023to 3 Jan 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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);

Who cannot join

  • 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
Show all 19Show fewer
  • 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)

Trial locations and contacts

28 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Bruno LEVY, Pr contact

+33 3 83 15 40 84

b.levy@chru-nancy.fr

28 sites in 1 country

France28 sites, 28 recruiting

  • CHR Metz-Thionville, Mercy Hospital

    Ars-Laquenexy, Moselle, 57245

    Guillaume Louis, MD

    Guillaume Louis, MD

    Recruiting

  • CH Henri Duffaut, Avignon

    Avignon, Vaucluse, 84000

    Stéphane Andrieu, MD

    Stéphane Andrieu, MD

    Not yet recruiting

  • CHU Besançon Jean Minjoz Hospital

    Besançon, Doubs, 25000

    Hadrien WINISZEWSKI, MD

    Hadrien WINISZEWSKI, MD

    Recruiting

  • CHU Bordeaux - Hopital haut-leveque

    Bordeaux, Gironde, 33600

    Edouard Gerbaud, MD

    Edouard Gerbaud, MD

    Recruiting

  • CHU Bordeaux

    Bordeaux

    Alexandre OUTARRA, MD-PhD

    Alexandre OUTARRA, Md-PhD

    Recruiting

  • Hospices Civils de Lyon - Louis Pradel Hospital

    Bron, Rhône, 69500

    Bertrand SCHEPPLER, MD, +33 4 72 11 80 88, bertrand.scheppler01@chu-lyon.fr

    Bertrand SCHEPPLER, MD

    Recruiting

  • CHU Caen

    Caen, Calvados, 14000

    Katrien Blanchart, MD

    Katrien Blanchart, MD

    Not yet recruiting

  • APHP, Henri Mondor Hospital

    Créteil, Val de Marne, 94010

    Raphaëlle HUGUET, MD, +33 1 49 81 21 11, raphaelle.huguet@aphp.fr

    Raphaelle HUGUET, MD

    Recruiting

  • HENRI MONDOR -réanimation

    Créteil

    Armand MEKONTSO DESSAP, MD-Phd, +33 1 49 81 21 11, armand.dessap@aphp.fr

    Armand MEKONTSO DESSAP, MD-PhD

    Not yet recruiting

  • CHU Dijon

    Dijon, Côte d'Or, 21000

    Jean-Pierre Quenot, MD-PhD

    Jean-Pierre Quenot, MD-PhD

    Recruiting

  • Chu Dijon

    Dijon

    Pierre Grégoire GUINOT, MD-PhD

    Pierre Grégoire GUINOT, MD-PhD

    Recruiting

  • CHU Grenoble, Michallon Hospital

    La Tronche, Isère, 38043

    Joanna Bougnaud, MD

    Joanna Bougnaud, MD

    Recruiting

  • CHU Grenoble -USIC

    La Tronche, 38700

    Nicolas PILIERO, MD

    Nicolas PILIERO, MD

    Recruiting

  • CHRU Lille, Cœur Poumon Institute

    Lille, Nord, 59000

    Gilles LEMESLE, MD-PhD

    Gilles LEMESLE, MD-PhD

    Recruiting

  • CHU Limoges, Dupuytren Hospital

    Limoges, Haute-Vienne, 87000

    Philippe Vignon, MD

    Philippe Vignon, MD

    Recruiting

  • AP-HM, Nord Hospital, Marseille

    Marseille, Bouches du Rhône, 13015

    Laurent Bonello, MD

    Laurent Bonello, MD

    Recruiting

  • AP-HM CHU la Timone

    Marseille, 13385

    Florent ARREGLE, MD

    Florent ARREGLE, MD

    Recruiting

  • CHU Montpellier, Arnaud de Villeneuve Hospital

    Montpellier, Hérault, 34090

    François Roubille, MD

    François Roubille, MD

    Recruiting

  • CHU Montpellier -hôpital Arnaud de Villeneuve

    Montpellier, 34295

    Philippe GAUDARD, MD-PhD

    Philippe GAUDARD, MD-PhD

    Recruiting

  • CHU Nantes

    Nantes, Loire-Atlantique, 44000

    Julien Plessis, MD

    Julien Plessis, MD

    Recruiting

  • CHU Nîmes, Carémeau Hospital

    Nîmes, Gard, 30029

    Benoît Lattuca, MD

    Benoît Lattuca, MD

    Recruiting

  • APHP, La Pitié Salpêtrière (medical intensive care unit)

    Paris, Paris, 75013

    Alain Combes, MD

    Alain Combes, MD

    Recruiting

  • CHU Rennes, Pontchaillou Hospital

    Rennes, Ille et Vilaine, 35000

    Abdelkader BAKHTI, MD

    Abdelkader BAKHTI, MD

    Recruiting

  • Chu Rouen

    Rouen

    Emmanuel BESNIER, MD-PhD

    Emmanuel BESNIER, MD-PhD

    Recruiting

  • CHRU Strasbourg -Nouvel Hôpital Civil

    Strasbourg, Bas-Rhin, 67091

    Ferhat MEZIANI, MD-PhD

    Ferhat MEZIANI, MD-PhD

    Recruiting

  • HU Strasbourg USIC

    Strasbourg

    Olivier MOREL, MD PhD, +33 3 88 11 67 68, olivier.morel@chru-strasbourg.fr

    Olivier MOREL, MD-pHD

    Not yet recruiting

  • CHU de Toulouse

    Toulouse, Haute-Garonne, 31059

    Clément Delmas, MD

    Clément Delmas, MD

    Recruiting

  • CHRU Nancy

    Vandœuvre-lès-Nancy

    Bruno Lévy, Prof

    Bruno LEVY, Prof

    Recruiting

Other trials in France

About this study

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.

Being tested
Levosimendan 2.5 MG/ML Injectable Solution, Placebo
Keywords
heart failure, levosimendan
Medical subject headings
Shock, Cardiogenic, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Levosimendan 2.5 MG/ML Injectable SolutionDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT04020263
Study groupRoleWhat they receive
LevosimendanExperimentalExperimental group: patients with cardiogenic shock treated with levosimendan in addition to the conventional strategy.
Receives: Drug: Levosimendan 2.5 MG/ML Injectable Solution
PlaceboPlacebo comparatorControl group: Patients with cardiogenic shock treated with placebo (Cernevit/Soluvit) in addition to the conventional strategy.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of All-cause mortality

    Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)

    Measured: Day 30 following randomization

  2. Proportion of Extra Corporel Life Support implantation

    Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)

    Measured: Day 30 following randomization

  3. Proportion of Dialysis

    Composite endpoint (i.e. All-cause Mortality and/or Extra Corporel Life Support implantation and/or dialysis)

    Measured: Day 30 following randomization

Secondary outcomes (41)

  1. 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).

    Measured: Day 90

  2. 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).

    Measured: Day 90

  3. 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).

    Measured: Day 90

  4. 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).

    Measured: Day 90

  5. 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).

    Measured: Day 90

  6. Proportion of death.

    Measured: Day 90

  7. Proportion of Extra Corporel Life Support implantation

    Measured: Day 90

  8. Proportion of dialysis

    Measured: Day 90

  9. Proportion of cardiac transplantation

    Measured: Day 90

  10. Proportion of escalation to permanent Left Ventricular Assist Device

    Measured: Day 90

  11. Proportion of stroke

    Measured: Day 90

  12. Proportion of recurrent myocardial infarction

    Measured: Day 90

  13. Proportion of urgent coronary revascularization

    Measured: Day 90

  14. Proportion of re-hospitalization for heart failure

    Measured: Day 90

  15. Proportion of All-cause mortality

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90.

    Measured: Day 90

  16. Proportion of Extra Corporel Life Support implantation

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90.

    Measured: Day 90

  17. Proportion of Dialysis

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis on day 90.

    Measured: Day 90

  18. Number of dobutamine free days

    Measured: From randomization to day 30

  19. Number of vasopressors free days

    Measured: From randomization to day 30

  20. Number of ventilatory free days

    Measured: From randomization to day 30

  21. Number of renal replacement free days

    Measured: From randomization to day 90

  22. Lactate clearance

    Measured: from randomization to day 7

  23. Duration of intensive care unit stay

    Measured: Up to Intensive Care Unit discharge (assessed up to 1 month)

  24. Duration of hospitalization

    Measured: Up to hospitalization discharge (assessed up to 1 month)

  25. Proportion of All-cause mortality

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis

    Measured: days 7, 60, and 180 days and 12 months

  26. Proportion of Extra Corporel Life Support implantation

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis

    Measured: days 7, 60, and 180 days and 12 months

  27. Proportion of dialysis

    Composite endpoint of all-cause mortality and/or ECLS requirement and/or dialysis

    Measured: days 7, 60, and 180 days and 12 months

  28. Number of renal replacement free days

    Measured: D 30, 60, 180 and at 12 months

  29. Proportion of death

    Measured: days 180 and at 12 months

  30. Proportion of Extra Corporel Life Support implantation

    Measured: days 180 and at 12 months

  31. Proportion of dialysis

    Measured: days 180 and at 12 months

  32. proportion of cardiac transplantation

    Measured: days 180 and at 12 months

  33. proportion of escalation to permanent left ventricular assist device

    Measured: days 180 and at 12 months

  34. Proportion of stroke

    Measured: days 180 and at 12 months

  35. Proportion of recurrent myocardial infarction

    Measured: days 180 and at 12 months

  36. Proportion urgent coronary revascularization

    Measured: days 180 and at 12 months

  37. proportion of re-hospitalization for heart failure

    Measured: days 180 and at 12 months

  38. 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)

    Measured: from randomization to intensive care unit discharge.

  39. 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

    Measured: from randomization to intensive care unit discharge.

  40. 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.

    Measured: Day 30

  41. 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

    Measured: At intensive care unit discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2019
  2. Study start3 Jul 2023
  3. Primary completion3 Feb 2027 (estimated)
  4. Study completion3 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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).
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
610 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04020263
Sponsor's protocol ID
2024-513811-29-00
Other IDs
2024-513811-29-00
Acronym
LevoHeartShock
Status last verified
Jul 2025
First submitted
28 Jun 2019
Last updated
5 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Levosimendan 2.5 MG/ML Injectable Solution in people with Cardiogenic Shock, run by Pr Bruno LEVY at 28 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bruno LEVY, Pr (+33 3 83 15 40 84, b.levy@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of All-cause mortality (time frame: Day 30 following randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04020263.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.

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