Simdax (levosimendan IV) / AbbVie, Orion Corp, Tenax Therap - LARVOL DELTA

Levosimendan in Acute Decompensated Heart Failure (clinicaltrials.gov) - P2/3 | N=332 | Not yet recruiting | Sponsor: Chittagong Medical College

HEOR • New P2/3 trial • Real-world evidence • Cardiovascular • Congestive Heart Failure • Heart Failure

Levosimendan ameliorates cardiomyocyte injury and mitochondrial dysfunction in an Nrf2-dependent manner in mice with sepsis-induced cardiomyopathy. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "Notably, the protective effects of LEVO on cardiomyocyte viability and mitochondrial function are significantly diminished following Nrf2 inhibition or Nrf2 knockout (KO). Collectively, these findings demonstrate that LEVO mitigates cardiomyocyte injury and mitochondrial dysfunction in SIC through an Nrf2-dependent mechanism."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Metabolic Disorders • Septic Shock • IL6

Hemodynamic effects of levosimendan in low cardiac output syndrome post-CABG refractory to standard inotropic therapy. (PubMed, Med Klin Intensivmed Notfmed) - "This retrospective single-center case series suggests that levosimendan may be associated with hemodynamic improvement in patients with LCOS after CABG who are unresponsive to standard therapy. However, due to the absence of a control group and the retrospective design, these findings should be considered exploratory and hypothesis-generating."

Journal • Cardiovascular • Coronary Artery Disease • Hypotension

Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: Research Summary. (PubMed, JAMA) - No abstract available

Journal • Cardiovascular

Levosimendan and Weaning From VA-ECMO. (PubMed, JAMA) - No abstract available

Journal

Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial. (PubMed, JAMA) - P3 | "Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo. ClinicalTrials.gov Identifier: NCT04728932."

Clinical • Journal • Cardiovascular • Critical care • Inflammation • Myocardial Infarction

Prognosis and Risk Stratification of Patients with Advanced Heart Failure Followed-Up on an Outpatient Clinic. (PubMed, Biomedicines) - "Three distinctive patterns of management were recognized and assessed: intermittent levosimendan administration to 33 patients, intermittent intravenous furosemide administration to 17 patients, and 45 patients were followed up exclusively on an outpatient basis with frequent visits... AdvHF patients represent a complex population requiring close follow-up and novel strategies to improve survival. Larger studies are needed to refine and update predictive scores in this population."

Journal • Atrial Fibrillation • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Heart Failure • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases

Efficacy of levosimendan for acute decompensated heart failure with preserved ejection fraction in the elderly: a single-center retrospective analysis. (PubMed, BMC Cardiovasc Disord) - "For older patients with acute HFpEF combined with more comorbidities, although levosimendan may transiently improve hemodynamics and functional capacity in the acute phase, it fails to demonstrate long-term prognostic benefits. The clinical benefit of this drug may be limited to select patients, and its clinical application may lack cost-effectiveness for broader application."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure

Utilization patterns and determinants of guideline-recommended therapies for acute heart failure in Denmark. (PubMed, Eur Heart J Acute Cardiovasc Care) - "Loop diuretics were widely used, while vasodilators, inotropes, and vasopressors had lower utilization. The observed variation in treatment reflects complexity of inpatient AHF management, warranting further studies to assess treatment outcomes."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease

Population Pharmacokinetics of Levosimendan and its Metabolites OR-1855 and OR-1896 in Critically Ill Adults, Neonates and Infants on Veno-Arterial ECMO. (PubMed, Clin Pharmacokinet) - "Our data indicate that levosimendan and its metabolites exhibit altered the pharmacokinetics in neonates/infants on VA-ECMO. Although some of these changes may be associated with ECMO, definitive conclusions on causality cannot be drawn, as age-dependent specific physiology and critically ill conditions may also contribute. These findings support the consideration of dose optimisation in this population. In adults, levosimendan pharmacokinetics seem unaffected, although metabolite concentrations appear slightly reduced compared with non-critically ill patients with heart failure."

Journal • PK/PD data • Cardiovascular • Congestive Heart Failure • Critical care • Heart Failure

Levosimendan in Cardiac Arrest (LeiCA): Protocol for a Randomized, Double-Blind, Phase II Clinical Trial. (PubMed, Acta Anaesthesiol Scand) - "The LeiCA pilot trial will investigate the effects of levosimendan as an adjunct to advanced life support for refractory OHCA. The results will inform the design of a definitive multicenter trial."

Clinical • Clinical protocol • Journal • P2 data • Cardiovascular • Congestive Heart Failure • Heart Failure

WEANLESS: Shorter Weaning From Invasive Ventilation With Levosimendan (clinicaltrials.gov) - P4 | N=250 | Recruiting | Sponsor: Radboud University Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open

Levosimendan versus dobutamine in acute decompensated heart failure: systematic review and meta-analysis of randomised controlled trials. (PubMed, Heart) - "Levosimendan reduced short-term mortality and hospital stay compared with dobutamine in patients with ADHF, although the certainty of evidence was moderate for mortality and very low for hospital stay. Larger trials are needed to confirm these findings."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure

Clinical Importance of Phosphodiesterase 3 Inhibitors on Outcomes in Patients With Cardiogenic Shock　- A Systematic Review. (PubMed, Circ Rep) - "One RCT compared milrinone with dobutamine (DOB), and another compared enoximone with levosimendan. Meta-analysis revealed that PDE3i were neither superior nor inferior for the outcomes in the total cohort (odds ratio [OR] 1.47, 95% confidence interval [CI] 0.35-6.26 for early deaths; OR 1.14, 95% CI 0.42-3.14 for cardiac arrest; OR 1.53, 95% CI 0.80-2.92 for the initiation of renal replacement therapy). The present systematic review revealed no difference in outcomes, early deaths, cardiac arrest and initiation of renal replacement therapy when using PDE3i in patients with CS treated with or without other inotropes."

Journal • Cardiovascular

Cardiogenic shock: Who benefits from heart replacement therapy? (PubMed, Int J Cardiol) - "In this large cohort of unselected CS patients, HRT was performed in more than 10 % of cases (6.3 % in-hospital and 3.8 % between discharge and 1-year follow-up), with a comparable in-hospital mortality rate to non-HRT patients. Further studies are needed to optimize the selection criteria for HRT in CS patients."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation

Effects of Xuebijing combined with levosimendan on immune function and coagulation function in sepsis patients with myocardial injury. (PubMed, J Thromb Thrombolysis) - "Levels of NO, VEGF, PLT, Fib, CD4+, CD4+/CD8+ ratio, MAP and CVP were higher in the combination group than in the control group (all P < 0.05). The combination of XBJ and levosimendan improves coagulation function, regulates immune function, enhances vascular endothelial function and hemodynamics, reduces inflammation, and alleviates myocardial injury."

Journal • Infectious Disease • Oncology • Septic Shock • CD4 • CD8 • CRP • EDN1 • TNFA • TNNI3

Safety and Efficacy of Levosimendan for Acute Ischemic Stroke: A Randomized Controlled Clinical Trial (ChiCTR) - P4 | N=100 | Not yet recruiting | Sponsor: the First Hospital of Jilin University.; the First Hospital of Jilin University.

New P4 trial • Cardiovascular • Ischemic stroke

Phenotype-Guided Outpatient Levosimendan as a Bridge-to-Transplant in Low-Output Advanced Heart Failure: A Single-Center Cohort. (PubMed, J Pers Med) - " By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Transplantation

DIVERGENT HEMODYNAMIC AND OXYGENATION OUTCOMES OF VASODILATORS FOR PULMONARY HYPERTENSION IN ARDS: A NETWORK META-ANALYSIS (CHEST 2025) - "A frequentist network meta-analysis integrated with Bayesian hierarchical modeling compared inhaled nitric oxide (NO), prostacyclin (PGI2), levosimendan, nitroglycerin (NTG), prostaglandin E1 (PGE1), liposomal PGE1, and placebo. No vasodilator demonstrated universal superiority. Clinicians must prioritize outcome-specific therapy: NO/ PGI2 for hemodynamic stabilization, levosimendan for isolated PVR reduction, and liposomal PGE1 for refractory hypoxemia. Critical efficacy dichotomies exist—PGI2 improves cardiac output but impairs oxygenation, necessitating personalized treatment."

Retrospective data • Acute Respiratory Distress Syndrome • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

COMPARATIVE EFFICACY OF LEVOSIMENDAN AND DOBUTAMINE IN SEPSIS-INDUCED CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS (CHEST 2025) - "Our findings support the preferential use of levosimendan over dobutamine in SICM patients, where its unique mechanisms may offer advantages beyond conventional beta-adrenergic stimulation. However, given the variability in patient response and the need for personalized hemodynamic management, future large-scale randomized controlled trials are needed to consolidate these findings and establish definitive treatment guidelines. CLINICAL IMPLICATIONS: Patients with sepsis-induced cardiomyopathy may experience greater benefits from levosimendan than dobutamine, particularly in terms of improving myocardial function."

Retrospective data • Review • Cardiomyopathy • Cardiovascular • Infectious Disease • Metabolic Disorders • Septic Shock

Impact of Pre-Heart Transplant Levosimendan Administration on Post-Transplant Vasoplegia and Primary Graft Dysfunction. (PubMed, Clin Transplant) - "This study evaluated whether giving levosimendan before HT affects early post-transplant complications. Among 598 patients, 94 received levosimendan within a month before surgery. Results showed no significant differences in rates of vasoplegia, severe primary graft dysfunction, or mortality. Levosimendan use appears safe in the immediate pre-transplant setting."

Journal • Observational data • Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation

Levosimendan in Decompensated Heart Failure with Reduced Ejection Fraction in Older Adults: A Systematic Review of Safety and Efficacy. (PubMed, Medicines (Basel)) - "Levosimendan may improve short-term hemodynamic parameters in older adults with decompensated HFrEF, but the available evidence is limited and heterogeneous. Its effects on mortality and rehospitalization remain inconclusive. Clinical use should be individualized and closely monitored, particularly in frail patients."

Journal • Review • Cardiovascular • Congestive Heart Failure • Geriatric Disorders • Heart Failure • Hypotension

Cardiac contractility modulation therapy and levosimendan: two brothers in arms against heart failure with preserved ejection fraction. (PubMed, J Cardiovasc Med (Hagerstown)) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

A hypoxia-on-a-chip platform for modeling ischemic arrhythmogenesis and evaluating the effects of levosimendan and OR-1896 on ischemic human iPSC-derived cardiomyocytes. (PubMed, Front Bioeng Biotechnol) - "This study provides the first comprehensive evidence of the cardioprotective and antiarrhythmic properties of levosimendan's metabolite, demonstrating its ability to reduce hypoxia-induced cellular injury and correct abnormal Ca2+ transients. These findings highlight the therapeutic potential of levosimendan and its clinically significant long-acting metabolite, OR-1896, in the treatment of cardiac ischemia."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Myocardial Ischemia

Levosimendan versus dobutamine in septic cardiomyopathy: a randomized clinical trial on cardiac function and safety. (PubMed, Front Cardiovasc Med) - P4 | "Further studies are needed to evaluate the long-term effects of levosimendan on clinical outcomes in this patient population. ChiCTR2500101261."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Musculoskeletal Diseases • Orthopedics • Septic Shock • TNNI3