Application of Stimulated Immune Response Change to Predict Outcome of Patient With Severe Sepsis (SIRCSS)

December 5, 2018 updated by: Chang Gung Memorial Hospital

Persistence of a marked compensatory anti-inflammatory innate immune response after an insult is termed immunoparalysis. There is no biomarker available to determine the immune status of patient. Thus, the need for early and definite diagnosis of immune status of patient with sepsis, as well as the identification of patients at risk of evolving with severe organ dysfunctions, is crucial.

Most important of all, speed is the key to survival. Therefore, it of crucial importance to identify which patient characteristic determines the poor prognosis. Early intervention can improve the prognosis. Investigators foresee an urgent need to identify predictors for mortality in severe sepsis, including clinical factors or immune status. Recently, the PIRO model has been proposed as a way of stratifying septic patients according to their Predisposing condition, the severity of Infection, the Response to therapy and the degree of Organ dysfunction. The immune status may be associated with above model. However, there is paucity data addressing this issue. In this study, investigators will also analyze the progression of patient condition during treatment and the associated immune status change. In the future, Investigators hope the determination of immune status may contribute to this model of classification rather than just being used as prognostic markers. Despite the advances in the knowledge of the basic processes that trigger and sustain the systemic inflammatory response in sepsis, the search for a "magic bullet" to treat this syndrome has been frustrating. The incidence of severe sepsis and septic shock still remains quite high, as does its mortality, which has decreased very little over the past decades.

Study Overview

Status

Unknown

Conditions

Detailed Description

Binding of TLRs to epitopes on microorganisms stimulates intracellular signaling, increasing transcription of proinflammatory molecules such as tumor necrosis factor α (TNF-α) and interleukin-1β, as well as antiinflammatory cytokines such as interleukin-10. Macrophage dysfunction, as a component of immune suppression seen during trauma and sepsis, appears to be one of the contributing factors to morbidity and mortality. Critically ill patients demonstrating prolonged, severe reductions in monocyte HLA-DR expression or ex vivo tumor necrosis factor alpha production are at high risk for nosocomial infection and death. Most septic patients have decreasing cytokine levels at the time of treatment, suggesting a transition from a hyperinflammatory to a hypo-inflammatory state. Immunoparalysis is a potentially reversible risk factor for development of nosocomial infection in multiple organ dysfunction syndrome. Whole-blood ex vivo TNF alpha response is a promising marker for monitoring this condition. Investigators call it as "stimulated immune response". Toll-like receptors (TLRs) are a recently described family of immune receptors involved in the recognition of pathogen-associated molecular patterns (PAMPs). Lipopolysaccharide (LPS) is present in the outer membranes of Gram-negative bacteria and has been demonstrated to be responsible for the development of GNB-associated sepsis. Recognition of bacterial LPS by macrophages is a key component of host defense against infection by Gram-negative bacteria. A monocyte which encounters LPS should vigorously produce proinflammatory cytokines regardless of whether or not it has been exposed to LPS in the past. Sepsis induces suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Whether further ground can be gained by manipulating innate immunity is an important question waiting to be answered. Several strategies to enhance innate immunity have been tried in normal subjects, including using granulocyte colony-stimulating factor to increase the number and activation state of circulating neutrophils, and IFN-γ to enhance macrophage dependent immunity. Investigators will use this characteristic to assess patient's stimulated immune response. In addition, differences in the nature of the initiating agent causing sepsis and the lack of co-morbidities in the animal models probably contribute to some of the differences in animal studies and clinical trials in sepsis. Investigators need to address these important issues and work toward promoting immunologic homeostasis in the ICU. Here investigators performed a systematic study aimed at evaluating

  1. The diagnostic accuracy of stimulated immune response for predicting mortality;
  2. Whether trend change in stimulated immune response more useful for above prediction;
  3. Whether stimulated immune response can predict patients at risk of evolving with severe organ dysfunctions (the presence or development of severe sepsis or progression of organ dysfunctions within a 72-hr time period from biomarker checked along with treatment)

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Kaohsiung, Taiwan
        • Recruiting
        • Chang Gung Memorial Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study will be conducted at Kaohsiung Chang Gung Memorial Hospital. All adult patients presenting with sepsis or severe sepsis will be enrolled on admission to medical intensive units (total 34 beds). Sepsis and severe sepsis are defined as American College of Chest Physicians/Society of Critical Care Medicine consensus criteria for sepsis syndromes.

Description

Inclusion Criteria:

  • Severe sepsis
  • Septic shock

Exclusion Criteria:

  • Patients are < 18 yrs
  • Patients are immunocompromised (treatment with corticosteroids >1 mg/kg equivalent prednisone)
  • Bone marrow or organ transplant recipients,
  • Leucopenia [white blood cells count< 109/L] or neutropenia [polymorphonuclear granulocyte count <0.5 109/L]
  • Hematologic malignancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The diagnostic accuracy of stimulated immune response for predicting mortality
Time Frame: 4 weeks, up to 24 weeks
4 weeks, up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Whether trend change in stimulated immune response more useful for prediction mortality
Time Frame: 4 weeks, up to 24 weeks
4 weeks, up to 24 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Whether stimulated immune response can predict patients at risk of evolving with severe organ dysfunctions
Time Frame: 4 weeks, up to 24 weeks
4 weeks, up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

  • Principal Investigator: Wen-Feng Fang, M.D, Chang Gung Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2013

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

August 15, 2016

First Submitted That Met QC Criteria

August 29, 2016

First Posted (Estimate)

September 2, 2016

Study Record Updates

Last Update Posted (Actual)

December 7, 2018

Last Update Submitted That Met QC Criteria

December 5, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMRPG8B1073

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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