Effects of Levosimendan on Microcirculation in Septic Shock

Septic Shock Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00800306
• Other study ID #: 1102
• Status: Completed
• Phase: Phase 2
• First received: December 1, 2008
• Last updated: October 14, 2009
• Start date: November 2007
• Est. completion date: April 2009

Study information

• Verified date: October 2009
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2009
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• Levosimendan
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
• dobutamine
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.

Locations

Country	Name	City	State
Italy	Departement of Anesthesiology and Intensive Care of the University of Rome "La Sapienza" Viale del Policlinico 155	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI)		over a period of 36 hrs from the time of randomization	No
Secondary	Acid-base homeostasis		over a period of 36 hrs from the time of randomization	No
Secondary	Oxygen transport variables		over a period of 36 hrs from the time of randomization	No
Secondary	Functional capillary density (mm/mm2) (FCD)		over a period of 36 hrs from the time of randomization	No
Secondary	De Backer score		over a period of 36 hrs from the time of randomization	No
Secondary	Perfused Vessel Density (PVD) (mm/mm2)		over a period of 36 hrs from the time of randomization	No
Secondary	Proportion of Perfused vessels (%) (PPV)		over a period of 36 hrs from the time of randomization	No