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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

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

Recruiting
18 years and older
All
Phase 3

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Overview

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.

Eligibility

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)

Study details
    Cardiogenic Shock

NCT04020263

Pr Bruno LEVY

15 August 2025

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