Effects of Levosimendan on Microcirculation in Septic Shock

Phase 2

Completed

• Conditions: Septic Shock
• Interventions: Drug: Levosimendan; Drug: dobutamine

• Registration Number: NCT00800306
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

The present study was conducted as a prospective, randomized, controlled study to:

* investigate the effects of a combination of levosimendan and inhaled nitric oxide on systemic hemodynamics and microcirculation in patients with catecholamine-dependent septic shock;

* test the hypothesis that levosimendan plus inhaled nitric oxide may be effective in restoring microvascular function in septic shock.

Detailed Description

40 septic shock patients requiring norepinephrine to maintain mean arterial pressure between 65 and 75 mmHg despite adequate volume resuscitation will be enrolled in the study. After an initial hemodynamic resuscitation aimed at achieve a mean arterial pressure between 65 and 75 mmHg and a mixed venous oxygen saturation (SvO2) ≥ 65%, patients will be randomly allocated to be treated with either a) intravenous administration of levosimendan 0.2 µg∙kg-1∙min-1 for 24 hrs, b)intravenous administration of dobutamine 5 µg∙kg-1∙min-1 for 36 hrs(control; each n = 20). At the end of the first 24 hrs of the study period, both groups will receive inhaled nitric oxide at the concentration of 35 ppm for further 12 hrs. In all patients norepinephrine was titrated to maintain mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization and sublingual microvascular network will be obtained just before randomization (baseline) and then after 24 and 36 hours.

The sublingual microvascular network will be studied using the sidestream dark field (SDF) imaging. The device will be applied on the lateral side of the tongue, in an area approximately 2-4 cm from the tip of the tongue. Sequences of 10 secs from eight adjacent areas will be recorded on disk using a personal computer. These sequences will be later analyzed by an investigator blinded to the patient's diagnosis and therapy.

Study Timeline

• Study Start: 2007-11
• Primary Completion: 2008-02
• Study First Submitted: 2008-12-01
• Study First Submitted QC: 2008-12-01
• Study First Posted: 2008-12-02
• Study Completion: 2009-04
• Status Verified: 2009-10
• Last Update Submitted: 2009-10-14
• Last Update Posted: 2009-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Clinical diagnosis of Septic shock
• Vasopressor support to maintain mean arterial pressure (MAP) between 65 and 75 mmHg despite adequate volume resuscitation (pulmonary artery occlusion pressure = 13-18 mmHg and central venous pressure = 8-12 mmHg)

Exclusion Criteria

• Pregnancy
• Age < 18 years
• Ventricular outflow tract obstruction
• Mitral valve systolic anterior motion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
levosimendan	Levosimendan	-
Control	dobutamine	-

Primary Outcome Measures

Name	Time	Method
Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)	over a period of 36 hrs from the time of randomization

Secondary Outcome Measures

Name	Time	Method
Acid-base homeostasis	over a period of 36 hrs from the time of randomization
Oxygen transport variables	over a period of 36 hrs from the time of randomization
Functional capillary density (mm/mm2) (FCD)	over a period of 36 hrs from the time of randomization
De Backer score	over a period of 36 hrs from the time of randomization
Perfused Vessel Density (PVD) (mm/mm2)	over a period of 36 hrs from the time of randomization
Proportion of Perfused vessels (%) (PPV)	over a period of 36 hrs from the time of randomization

Trial Locations

Locations (1)

Departement of Anesthesiology and Intensive Care of the University of Rome "La Sapienza" Viale del Policlinico 155; 🇮🇹 Rome, Italy