Biomarkers in Infection

Sepsis Clinical Trial

Official title:

Early Detection of Inflammatory Biomarkers in Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02545478
• Other study ID #: 2005P000116
• Status: Recruiting
• Start date: April 2006
• Est. completion date: April 2023

Study information

• Verified date: January 2020
• Source: Beth Israel Deaconess Medical Center
• Contact: Nathan Shapiro, MD MPH
• Phone: 617-754-2343
• Email: nshapiro[@]bidmc.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this investigation is to evaluate how early biomarkers of infection and inflammation perform in identifying patients at risk for poor outcome in sepsis and septic shock.

Description:

The body's immune system and a subsequent inflammatory response are triggered during infection. The detection of an activated immune system, and an indication of the degree of the host response, is helpful to the clinician both in assessing the severity of infection and in patient treatment and management. Currently, the white blood cell count and the differential are the most common laboratory parameters for measuring host response. The sedimentation rate and CRP are also used to detect inflammation. However, these tests are all imperfect predictors, and a test providing a better assessment of immune response would be helpful to the clinician in patient care. Additionally, understanding host response to infection may be helpful in understanding the biology and pathophysiology of sepsis. There are other biomarkers and inflammatory markers that may be found early in the initial presentation of infection such as cytokines (VEGF IL-1,IL-4,IL-6, IL-10, PAF, TNF, lectins iNoS,etc.) and clotting factors (protein C, d-dimer, complements involved in the clotting cascade, CRP, etc) that may provide a means of early detection of systemic inflammation, cell dysfunction, and related conditions. Early identification of patients at risk for systemic inflammatory syndromes, sepsis and septic shock may help direct patients to earlier antibiotic administration and early intervention with goal directed therapy. It may also serve as a tool for risk stratification when components such as age, comorbid illness and infection type are included.

The endothelium and endothelial cell markers are important in sepsis, yet a somewhat under-studied field of research. Additionally, the endothelium is a key regulator of the microcirculation, a place where oxygen diffusion occurs. One focus of this study is to measure endothelial markers (ie VEGF) and other cytokines with the goal of correlating these markers with severity of sepsis. Another focus is to study the response of various components in the blood, including the leukocytes, red cells, the endothelium, as well as cellular components such as the mitochondria. We will specifically look at alterations in thiamine, Vitamin D, CoQ10,l-carnitine and other nutrients as part of (and as related to) the body's response. Recently, a non-invasive method of assessing microvascular circulation by orthogonal polarization spectral (OPS) imagery has become available using a non-invasive technology known as orthogonal polarization spectroscopy. This technique enables direct visualization and quantification of microcirculatory blood flow, and represents an important surrogate outcome to which endothelial cell marker may be correlated. This will involve placing the microscopy probe gently against the sublingual mucosa and collecting a videotape of the circulation lasting about twenty seconds. This process involves minimal (or no) risk - it is akin to taking a temperature and uses no radiation. This videotape will be examined later by a novel software program that quantifies the circulation and used as an important surrogate outcome measure. Additionally, we are going to perform echocardiography to better understand the heart's response to sepsis, and correlated the molecular responses that we find with the changes in the responses by the heart.

This is a multicenter, observational pilot study which aims to evaluate how early biomarkers of infection an inflammation perform in identifying patients at risk for poor outcomes in sepsis and septic shock. The study will utilize a cohort of patients presenting to the ED with suspected infection as well as non-infected control population.

These patients will be compared with a non-infected population.

Enrolled subjects in the infected group will have blood samples and chart review obtained at enrollment, 24, 48 and 72 hours. For the control group, only a single blood draw will be collected at enrollment.

Enrolled subjects will also undergo physiologic assessments using echocardiography, Microscan, Non-invasive cardiac output monitor (NICOM), extremity temperature as well as End-Tidal C02 measurements if a trained researcher is present.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4200
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria for Infected subjects:

• Age 18 years of age or older

• Confirmed or suspected infection

Inclusion Criteria for Control Subjects:

• Age 18 years of age or older

• A non-infectious clinical presentation to include

• Normal white blood cell count ( > 4,000 and/or < 12,000)

• Normothermia ( > 96.5 and/or less 100.4)

• Absence of the following clinical complaints: productive cough, fever, pyuria, rash

• No evidence of acute coronary syndrome

Exclusion Criteria for Control Subjects:

• Suspected infection

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Inflammation
• Sepsis

Locations

Country	Name	City	State
Denmark	Aarhus universitetshospital	Aarhus
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New York Methodist Hospital	Brooklyn	New York
United States	Vanderbiltt University	Nashville	Tennessee
United States	St. Vincent's Hospital	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	28 day in-hospital mortality	participants will be followed up for 28 days	within 28 days after inclusion
Secondary	Organ Dysfunction assessed by Sepsis-related Organ Failure Assessment (SOFA) Score		within 24 hours