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Effects of Levosimendan on Microcirculation in Septic Shock

Levosimendan and Inhaled Nitric Oxide for Resuscitating the Microcirculation in Septic Shock. A Randomized Controlled Trial

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00800306
Enrollment
40
Registered
2008-12-02
Start date
2007-11-30
Completion date
2009-04-30
Last updated
2009-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Septic Shock

Keywords

sepsis, septic shock, microcirculation, levosimendan, dobutamine, inotropes, inhaled nitric oxide

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.

Interventions

DRUGLevosimendan

Intravenous administration of Levosimendan 0,2 µg•kg-1•min-1 for 24 hrs followed by the addition of 35 ppm of inhaled nitric oxide

DRUGdobutamine

Intravenous administration of dobutamine 5 µg•kg-1•min-1 for 36 hrs. At the end of the first 24 hrs drug infusion, inhaled nitric oxide at the concentration of 35 ppm will be added for further 12 hrs.

Sponsors

University of Roma La Sapienza
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

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

Secondary

MeasureTime frame
Oxygen transport variablesover 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
Acid-base homeostasisover 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
De Backer scoreover a period of 36 hrs from the time of randomization

Countries

Italy

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 30, 2026