Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock

Cardiogenic Shock Clinical Trial

Official title:

Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04917497
• Other study ID #: Levosimendan
• Status: Completed
• Start date: June 30, 2011
• Est. completion date: April 30, 2014

Study information

• Verified date: June 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: April 30, 2014
• Est. primary completion date: April 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Failure
• Acute Kidney Injury
• Cardio-Renal Syndrome
• Cardiogenic Shock
• Cardiorenal Syndrome
• Renal Insufficiency
• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Levosimendan
Levosimendan was administered according to a standardized treatment protocol. A total dose of 12.5mg or 25mg (corresponding to one or two ampoules) was given at an infusion rate of 0.05 µg/kg/min to 0.2µg/kg/min with or without a loading dose (6 µg/kg or 3 µg/kg over 10 minutes). The decision about total dose, infusion rate and loading dose was at the discretion of the treating physician.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

References & Publications (6)

Bragadottir G, Redfors B, Ricksten SE. Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit Care Med. 2013 Oct;41(10):2328-35. doi: 10.1097/CCM.0b013e31828e946a. — View Citation

Califf RM, Bengtson JR. Cardiogenic shock. N Engl J Med. 1994 Jun 16;330(24):1724-30. Review. — View Citation

Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation. 2003 Jun 24;107(24):2998-3002. Review. — View Citation

Papp Z, Édes I, Fruhwald S, De Hert SG, Salmenperä M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikström BG, Jörgensen K, Filippatos G, Parissis JT, González MJ, Parkhomenko A, Yilmaz MB, Kivikko M, Pollesello P, Follath F. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7. doi: 10.1016/j.ijcard.2011.07.022. Epub 2011 Jul 23. Review. — View Citation

Ronco C, House AA, Haapio M. Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med. 2008 May;34(5):957-62. doi: 10.1007/s00134-008-1017-8. Epub 2008 Feb 5. — View Citation

van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17;136(16):e232-e268. doi: 10.1161/CIR.0000000000000525. Epub 2017 Sep 18. Review. — View Citation

Outcome

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