Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock

Completed

• Conditions: Cardiorenal Syndrome; Acute Kidney Failure; Cardiogenic Shock
• Interventions: Drug: Levosimendan

• Registration Number: NCT04917497
• Lead Sponsor: University of Zurich

Brief Summary

To determine whether Levosimendan infusion in patients with cardiogenic shock and cardiorenal syndrome refractory to standard inotropic therapy, improves hemodynamics and renal function, whilst being safe.

Detailed Description

Cardiogenic Shock or the state of systemic hypoxia albeit initially preserved intra-vascular volume and intact vascular function, is solely the result of insufficient cardiac output \[1-2\]. The ensuing centralization and redistribution of blood-volume, is induced by a stimulation of the renin-angiotensin system, as well as vasopressin and endogenous catecholamine liberation \[2-3\]. Precipitating Cardiogenic Shock has a direct effect on the kidney, also called the cardiorenal syndrome \[4\].

The overall consensus for the therapy of cardiogenic shock is the use of inotropes to increase cardiac output and reverse organ hypoxia \[2\], nevertheless their increase of myocardial and glomerular oxygen consumption make them a double edged sword to use in cardiogenic shock and more prominently in cardiogenic shock coupled with pronounced cardiorenal syndrome.

Levosimendan is an inotropic agent that was developed for the treatment of severely decompensated heart failure. It exerts its inotropic effects primarily through sensitizing Troponin C to calcium and thereby increasing contraction of cardiac myofilaments during systole \[5\]. Unlike other inotropic agents, Levosimendan acts independently of the beta adrenergic receptor \[5\]. Additionally, the effect of Levosimendan could be beneficial for the kidneys function by decreasing pre-glomerular arteriolar vasotonus whilst keeping post-glomerular arteriolar vasotonus constant \[6\].

In light of the scarce but promising literature the question arises if Levosimendan can safely ameliorate cardiac and renal function concomitantly in patients presenting the combination of cardiogenic shock and cardiorenal syndrome.

Study Timeline

• Study Start: 2011-06-30
• Primary Completion: 2014-04-30
• Study Completion: 2014-04-30
• Study First Submitted: 2021-05-31
• Status Verified: 2021-06
• Study First Submitted QC: 2021-06-07
• Last Update Submitted: 2021-06-07
• Study First Posted: 2021-06-08
• Last Update Posted: 2021-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Levosimendan
• Cardiogenic Shock
• Continuous monitoring of cardiac output at the start of and during treatment with Levosimendan

Exclusion Criteria

• Extracorporal hemodynamic support or an implanted ventricular assist device
• Previous therapy with Levosimendan during the index hospitalization
• Refusal of participation in the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Levosimendan Treated Group	Levosimendan	All patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan.

Primary Outcome Measures

Name	Time	Method
Change in Fluid Balance	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of Fluid Balance post Levosimendan Infusion up until 120 hours
Change in Cardiac Index	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of Cardiac Index post Levosimendan Infusion up until 120 hours
Change in Mean Arterial Pressure	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of Mean Arterial Pressure post Levosimendan Infusion up until 120 hours
Change in Vasoactive/ Inotropic Dosage	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of Norepinephrine/ Dobuatmine Dosage post Levosimendan Infusion up until 120 hours
Change in Cardiac Preload Pressures	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of Wedge Pressure/ Central Venous Pressure post Levosimendan Infusion up until 120 hours
Change in Renal Function	Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion	Temporal development of eGFR (Creatinin estimated) post Levosimendan Infusion up until 120 hours