Effects of Levosimendan on Microcirculation in Septic Shock

This study has been completed.
Sponsor:
Information provided by:
University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT00800306
First received: December 1, 2008
Last updated: October 14, 2009
Last verified: October 2009
  Purpose

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.

Condition Intervention Phase
Septic Shock
Drug: Levosimendan
Drug: dobutamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Levosimendan and Inhaled Nitric Oxide for Resuscitating the Microcirculation in Septic Shock. A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Systemic hemodynamic and Microcirculatory flow index of small and medium vessels (MFI) [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acid-base homeostasis [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Oxygen transport variables [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Functional capillary density (mm/mm2) (FCD) [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • De Backer score [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Perfused Vessel Density (PVD) (mm/mm2) [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]
  • Proportion of Perfused vessels (%) (PPV) [ Time Frame: over a period of 36 hrs from the time of randomization ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: November 2007
Study Completion Date: April 2009
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: levosimendan 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
Active Comparator: Control Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00800306

Locations
Italy
Departement of Anesthesiology and Intensive Care of the University of Rome "La Sapienza" Viale del Policlinico 155
Rome, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Principal Investigator: Andrea Morelli, M.D. University of Rome "La Sapienza", Department of Anesthesiology and Intensive Care
  More Information

No publications provided by University of Roma La Sapienza

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrea Morelli, University of Rome "La Sapienza"
ClinicalTrials.gov Identifier: NCT00800306     History of Changes
Other Study ID Numbers: 1102
Study First Received: December 1, 2008
Last Updated: October 14, 2009
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
sepsis
septic shock
microcirculation
levosimendan
dobutamine
inotropes
inhaled nitric oxide

Additional relevant MeSH terms:
Shock
Shock, Septic
Infection
Inflammation
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Dobutamine
Nitric Oxide
Simendan
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-1 Receptor Agonists
Adrenergic beta-Agonists
Anti-Arrhythmia Agents
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiotonic Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Enzyme Inhibitors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014