LEVOSIMENDAN to Facilitate Weaning From ECMO in Severe Cardiogenic Shock Patients (LEVOECMO)

March 19, 2025 updated by: Assistance Publique - Hôpitaux de Paris

In the last decade, venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become the first-line therapy in patients with refractory cardiogenic shock. VA-ECMO provides both respiratory and cardiac support, is easy to insert, even at the bedside, provides stable flow rates, and is associated with less organ failure after implantation compared to large biventricular assist-devices that require open-heart surgery. In patients with potentially reversible cardiac failure (e.g. myocarditis, myocardial stunning post-myocardial infarction, post-cardiotomy or post-cardiac arrest), VA-ECMO might be weaned after a few days of support and used as a bridge to recovery.

Although considered as the ultimate life-saving technology for refractory cardiac failure, veno-arterial ECMO is still associated with severe complications. Specifically, excessive LV afterload and lack of LV unloading under VA-ECMO might induce LV stasis with thrombus formation, pulmonary edema, myocardial ischemia caused by ventricular distension and ultimately increase mortality. ECMO support also exposes to many complications such as infections, hemorrhage or peripheral vascular embolism. These complications are more frequent with prolonged support and are responsible for significant morbidity and mortality, prolonged ICU and hospital stays and higher costs.

Levosimendan, which acts to sensitize myocardial contractile proteins to calcium, improves cardiac contractility without increasing the intracellular calcium concentration. Unlike traditional inotropes such as dobutamine, levosimendan neither increases myocardial oxygen consumption nor impairs diastolic function or possess proarrhythmic effects. It also influences the opening of ATP-dependent potassium channels, including those in vascular smooth muscle cells, leading to coronary, pulmonary, and peripheral vasodilation and antiinflammatory, antioxidative, antiapoptotic, anti-stunning and cardioprotective effects. Additionally, Levosimendan which has a long lasting action (up to 7-9 d), resulting from the formation of active metabolite, may be used as a single 24h perfusion.

In recent preliminary studies, the drug was associated with accelerated weaning from VA-ECMO and even improved survival. Therefore, a multicenter randomized trial with sufficient statistical power is needed in refractory cardiogenic shock patients supported by VA-ECMO to test if the early administration of Levosimendan can facilitate and accelerate VA-ECMO weaning, and ultimately translate in significantly less morbidity, reduced ICU and hospital length of stays and associated costs.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
206

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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Study Contact

Study Contact

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Study Locations

  • France
      • Paris, France, 75013
        • Hopital Pitie Salpetriere
      • Paris, France
        • Hopital Europeen Georges Pompidou
    • Bordeaux
      • Pessac, Bordeaux, France
        • Hopital Du Haut-Leveque

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 specifications of emergency consent, randomization without the close relative or surrogate consent could be performed. Close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.

Exclusion Criteria:

  1. Age <18
  2. Pregnant or lactating women
  3. Initiation of VA-ECMO >48 h
  4. Resuscitation >30 minutes in the 48 hours before ECMO (cumulative low-flow time). If a low-flow episode occurs before the 48 hours window prior to ECMO, patients must fully recover consciousness to be randomized.
  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. 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. History of torsades de pointes in the 30 days prior to inclusion
  18. History of epilepsy
  19. Individuals under guardianship, or permanently legally incompetent adults
  20. Participation to another interventional study
  21. Patient with a weight over 180 kg
  22. Known hypersensitivity to polyvitamin CERNEVIT®
  23. In case of hypervitaminosis to any vitamin contained in this formulation,
  24. In case of severe hypercalcemia, hypercalciuria, treatment, pathology and/or disorders leading to severe hypercalcemia and/or hypercalciuria
  25. In combination with vitamin A or retinoids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Levosimendan
A continuous infusion of Levosimendan will be administered over 24 h, with no initial bolus. The starting infusion rate will be 0.15 µg/kg/min and will be increased to 0.20 µg/kg/min after 2 hours in the absence of rate-limiting side effects
Drug: Levosimendan
A continuous infusion of Levosimendan over 24h
Placebo Comparator: Placebo
A continuous infusion of Placebo will be administered over 24 h, with no initial bolus. The starting infusion rate will be 0.15 µg/kg/min and will be increased to 0.20 µg/kg/min after 2 hours in the absence of rate-limiting side effects
Drug: Placebo of Levosimendan
A continuous infusion of Placebo of Levosimendan over 24h

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Time to successful ECMO weaning within the 30 days following randomization
Time Frame: Day 30
Day 30

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Day 30, Day 60
Day 30, Day 60
Total duration of ECMO support
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Number of ECMO-free days
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Duration of ICU stay
Time Frame: Between inclusion and Day 60
Between inclusion and Day 60
Duration of hospitalization stay
Time Frame: Between inclusion and Day 60
Between inclusion and Day 60
Major adverse cardiovascular events
Time Frame: Day 30, Day 60
defined as death, cardiac transplant, escalation to permanent left ventricular assist device, stroke, dialysis, re-hospitalization for heart failure
Day 30, Day 60
Time to improvement in hemodynamic parameters
Time Frame: Between inclusion and Day 60
Between inclusion and Day 60
Time to hemodynamic stabilization
Time Frame: Between inclusion and Day 60
Between inclusion and Day 60
Days with organ failure asessed by sequential organ failure assessment
Time Frame: Between inclusion and Day 30
Between inclusion and Day 30
Duration of hemodynamic support with catecholamines
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Number of days alive without hemodynamic support
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Duration of mechanical ventilation
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Number of days alive without mechanical ventilation
Time Frame: Between inclusion and Day 30/Day 60
Between inclusion and Day 30/Day 60
Left ventricular function assessed with echocardiography
Time Frame: Day 30
Day 30
Incidence of adverse drug reactions
Time Frame: Between inclusion and Day 60
Between inclusion and Day 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 27, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 9, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 9, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 12, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P170914J
  • 2019-004319-29 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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