Levosimendan In Patients Undergoing LVAD Implantation

Pretreatment With Levosimendan In Patients Undergoing Left Ventricular Assist Device Implantation

According to the results from the literature, it has been shown that levosimendan usage 24-48 hours before LVAD implementation can improve short and long-term outcome in these patients regarding to the patients without preoperative pretreatment. The aim is to compare short and long-term outcome in patients who underwent to LVAD implementation and pretreated with levosimendan regarding the patient without pretreatment or with other medications.

Study Overview

• Status: Unknown
• Conditions: Right Ventricular Dysfunction; Left Ventricular Dysfunction; Biventricular Failure
• Intervention / Treatment: Drug: Levosimendan 2.5 MG/ML Injectable Solution

Detailed Description

Left ventricular assist device (LVAD) implantation is accepted for treatment of end-stage heart failure, in both as the bridging to heart transplantation or as the destination therapy. These patients have highly impaired systolic function which contributes to global heart dysfunction. The main complication is arising of pulmonary vascular pressures and pulmonary vascular resistance (PVR) and, consequently, right heart dysfunction. From the data in literature, RV dysfunction exist in approximately 25%-40% of patients with implanted LVAD, and in approximately 20%-30% of those died or have need for the RV assist device due to RV failure refractory to medications. Capability of the RV to maintain appropriate output and the fill of the LVAD is the main point for correct LVAD functioning and patients' early and late postoperative outcome. Preimplantation evaluation by echocardiography estimation of RV function, geometry and tricuspid valve function are the criteria for the diagnose of RV dysfunction. Laboratory analysis which can lead to the diagnose of RV dysfunction are also included in preimplantation evaluation. Specific inotropic therapy in patients with moderate or severe RV dysfunction and/or dilatation can improve RV function in preimplantation period. This is predominantly important in patients who were on the prolonged inotropic support with beta-agonist therapy before LVAD implantation and in whom their beta receptors are exhausted. The investigators will exam the hemodynamic effects of levosimendan administrated day before in patients underwent LVAD implantation. Further, investigators will analyze and evaluate early and late outcome in participants with implanted LVAD.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • Recruiting
    • Nikola Bradic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

In study will be observed all patients scheduled for LVAD implantation because of severe heart failure in which heart transplantation cannot be performed due to medical conditions. Further, in study will be observed all patients scheduled for LVAD implantation because of severe heart failure in which any other conservative/surgery therapy did not give positive results.

Description

Inclusion Criteria:

• All patients scheduled for LVAD implantation

Exclusion Criteria:

• Known patient's allergy on medication
• Patient's disagreement for the procedure

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levosimendan before LVAD implantation; Levosimendan use 24 hrs. before LVAD implantation	Drug: Levosimendan 2.5 MG/ML Injectable Solution; LVAD implantation; Other Names: Simdax
Dobutamine/milrinone before LVAD implantation; Dobutamine/milrinone use 24 hrs. before LVAD implantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of laboratory parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotropic day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, laboratory data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes and improvement/worsening of laboratory parameters depending of preoperative treatment.	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 1 and its changes is systemic vascular resistance index (SVRI); expressed by dyn·sec/cm5/m2	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 2 and its changes is pulmonary vascular resistance index (PVRI), expressed by dyn·sec/cm5/m2	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 3 and its changes is cardiac index (CI) expressed by L/min per m2	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 4 and its changes is right stroke work indexes (RVSWI) expressed by g·m/m2/beat	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 5 and its changes is left stroke work indexes (LVSWI) expressed by g·m/m2/beat	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 6 and its changes is stroke volume index (SVI) expressed by mL/m2	9 years
Measurement of hemodynamic parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotrope day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Further, hemodynamic data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes in hemodynamic outcome depending of preoperative treatment. Hemodynamic parameter 7 and its changes is right ventricular end-diastolic volume (RVEDV) expressed by mL.	9 years
Measurement of echocardiography parameters in patients who underwent LVAD implantation and pretreated with levosimendan or other inotropic day before surgery	Patients will be divided into two groups depending of administrated inotropic pretreatment (levosimendan or other inotropic medications) in preoperative period. Echocardiography data will be collected and analyzed three times in day before surgery and every four hours during first postoperative day after LVAD implantation to estimate changes and improvement/worsening of echocardiography parameters depending of preoperative treatment.	9 years

Collaborators and Investigators

• Sponsor: University Hospital Dubrava

Publications and helpful links

General Publications

• Sponga S, Ivanitskaia E, Potapov E, Krabatsch T, Hetzer R, Lehmkuhl H. Preoperative treatment with levosimendan in candidates for mechanical circulatory support. ASAIO J. 2012 Jan-Feb;58(1):6-11. doi: 10.1097/MAT.0b013e318239f401.
• Theiss HD, Grabmaier U, Kreissl N, Hagl C, Steinbeck G, Sodian R, Franz WM, Kaczmarek I. Preconditioning with levosimendan before implantation of left ventricular assist devices. Artif Organs. 2014 Mar;38(3):231-4. doi: 10.1111/aor.12150. Epub 2013 Oct 22.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2009
• Primary Completion (ANTICIPATED): December 31, 2020
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: June 24, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (ACTUAL): September 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 3, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Heart failure; Left ventricular dysfunction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Ventricular Dysfunction, Right; Ventricular Dysfunction, Left; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: UH Dubrava

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No