Endotoxin Activity Assay and Microcirculation in Severe Sepsis

Endotoxin Activity Assay and Microcirculation Examination in Patients With Severe Sepsis

Endotoxin is the major mediator of sepsis resulted from systemic inflammatory response syndrome induced by gram-negative bacteria infection. The endotoxin related inflammatory response and hypercoagulation can result in microcirculatory dysfunction. When microcirculatory dysfunction is severe, it can induce multiple organ dysfunction syndrome and death. This is a prospective observational study, and it will not influence the sepsis treatment decision of the medical care team. The critically ill severe sepsis patients will be enrolled only if they meet all inclusion criteria, do not meet any exclusion criteria and sign the consent form after explanation of the aim and process of the trial by the primary investigator or research personnel. After enrollment, the patient will receive serum assay of endotoxin activity (EAA) and endocan level. The patient will also receive examination of sublingual microcirculation by using the incident dark field video microscope. After 24 hours, the patient will receive assay of endocan level and examination of sublingual microcirculation. This study will record the vital signs, laboratory data, dose of vasopressors and inotropic agents, and severity of organ dysfunction. After 28 days, this study will check the survival, stay of intensive care, stay of hospital, ventilator day, and the results of culture of pathogens. The patients will be assign to the following three groups by the EAA level: low EAA group (< 0.40 EAA units); intermediate EAA group (0.40-0.59 EAA units); and high EAA group (≧ 0.60 EAA units). This grouping will be used for statistical analysis and comparison. The primary goal of this study is to investigate the difference of the prevalence of gram-negative bacteria infection, pathogen, infection source, microcirculation, the severity of disease, and the prognosis among these three groups.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Other: Severe sepsis management

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe sepsis

Description

Inclusion Criteria:

• patients with the following infections: intraabdominal infection, pneumonia, urinary tract infection, blood stream infection, or wound infection

• patients must also meet any one of the following criteria for severe sepsis

  • SBP < 90 mm Hg, MAP < 65 mm Hg, or requirement of vasopressors or inotropics
  • PaO2/FiO2 < 300
  • Creatinine level > 2 mg/dL or increase > 0.5 mg/dL; or urine output < 0.5 mL/kg/h more than 2 hours
  • Bilirubin level > 4 mg/dL
  • Platelet count < 100 k/uL or decrease more than 50%
  • INR > 1.5 or aPTT > 60 sec
  • GCS < 13 or 9T
  • Lactate > 2 mmol/L (with pH < 7.3 or base excess < -5 mmol/L)

Exclusion Criteria:

• younger than 20 yeras old or greater than 99 years old
• the onset of severe sepsis before enrollment is greater than 24 hours
• pregnant
• have received plymyxin-B hemoperfusion within 24 hours before enrollment
• non-native speaker

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low EAA; Endotoxin Activity Assay [EAA] level < 0.40 EAA units	Other: Severe sepsis management
Intermediate EAA; Endotoxin Activity Assay [EAA] level between 0.40-0.59 EAA units	Other: Severe sepsis management
High EAA; Endotoxin Activity Assay [EAA] level >= 0.60 EAA units	Other: Severe sepsis management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of the prevalence of gram-negative bacteria infection	Compare the prevalnce of gram-negative bacteria infection among the three groups	At enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality		28 days
Difference of Total small vessel density	Total small vessel density will be measured by incident dark field video microscope. Compare the difference among the three groups.	At Enrollment
Difference of Perfused small vessel density	Perfused small vessel density will be measured by incident dark field video microscope. Compare the difference among the three groups.	At enrollment
Endocan level	Endocan level will be measured by Human Endocan kit. Compare the difference among the three groups.	At enrollment
SOFA score	Compare the Sequential Organ Failure Assessment score among the three groups	At enrollement

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): May 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimate): May 22, 2015

Study Record Updates

• Last Update Posted (Estimate): December 18, 2015
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: 201503015RINB