Clinical Evaluation of Novel Biomarkers in Patients With Septicemia

Study Overview
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Brief Summary
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The protein ST2 is a member of the interleukin-1 receptor family. Blood concentrations of the soluble isoform of ST2 (sST2) are increased in inflammatory and heart diseases and are considered a prognostic marker in both. The Presage™ST2 assay was recently shown to meet the needs of quality specifications of laboratory medicine. Soluble urokinase plasminogen activator receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. Both sST2 and suPAR have recently been introduced as sensitive biomarkers for patients with septicemia. Both may be promising or even superior alternatives to currently established sepsis markers leading to an improvement of outcome in patients with septicemia. However, a clinical study which clarifies kinetics of values over time/possible correlation with causative pathogen/progress/deterioration of septic patients is urgently needed before these biomarkers can be established in clinical routine. Primary study objectives To clinically evaluate sST2 and suPAR in patients with bacteremia /septicemia. To correlate results with causative bacterial organisms, response to or failure of antiinfective treatment, severity of clinical status as well as outcome. To study the kinetics of the test results and to correlate the sST2/suPAR results with other well established infection markers (e.g. C-reactive protein, procalcitonin, blood counts). Natural endpoints of the study will be patient's death or complete recovery. This is an explorative study. To meet the objectives both novel biomarkers will be clinically evaluated in a cohort of 500 in-patients with septicemia at the University Hospital Graz. Starting the day a patient's blood culture turned positive the investigators will collect samples every 12h within the first two days and then every 24h.Measurement of sST2 and suPAR values will be done retrospectively. To analyze clinical sensitivity/specificity of the novel biomarkers sST2 and suPAR as prognostic factors for development of bacteremia/septicemia, a second cohort consisting of 250 in-patients will be investigated in a longitudinal matter. Patients without a previous positive blood culture test during the current episode of disease for which blood cultures are ordered by a physician will be included and sST2 and suPAR levels will be determined from samples taken simultaneously with this first blood cultures.

Detailed Description
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The two most common causative pathogens of septicemia (Escherichia coli and Staphylococcus aureus) as well as cases of fungemia (Candida spp., Aspergillus spp., and others) will be included in the first study group. At our hospital the estimated yearly cases of bacteremia/fungemia (230 for Escherichia coli, 150 for Staphylococcus aureus, and 50 for fungi) will be included in the first study group. Furthermore, the two biomarkers will be determined in 70 cases of septicemia with other bacterial pathogens and sepsis due to viral pathogens or viremia for evaluation of further clinical impact of these two biomarkers.

Official Title
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Clinical Evaluation of Novel Biomarkers for Diagnosis, Therapy- Monitoring and Prognosis of Outcome in Patients With Septicemia

Conditions
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Sepsis, Bacteremia, Fungemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients above 18 years Exclusion Criteria: Patients < 18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>All patients >18 years admitted to the University Hospital Graz, Austria, with positive blood cultures tested in the Microbiology Laboratory, Department of Internal Medicine, Medical University Graz, or the Institute for Hygiene, Microbiology and Environmental Medicine, Medical University Graz, are screened for study inclusion. Patients eligible for the study have to have Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Streptococcus pneumoniae, Klebsiella pneumoniae or medically relevant fungi / viral pathogens identified as causative pathogen. The estimated total number of patients included in this first study cohort will be 500. | |
| Cohort 2<br>All patients >18 years admitted to the University Hospital Graz, Austria, will be screened for study inclusion if the attending emergency department physicians on the very first visit suspects bacteremia/fungemia/sepsis and consecutively orders blood cultures. Patients will be included in this second cohort if these initially taken blood culture turns positive (n=200) or stays negative (n=50) at the Microbiology Laboratory, Department of Internal Medicine, Medical University Graz. As soon as the number of 50 is reached for the control group enrollment will be stopped for this group. As soon as the proposed number of 250 patients is reached enrolment for this second cohort will be stopped. Patients enrolled in cohort 2 may also be consecutively enrolled in cohort 1. | |
| Validation Cohort<br>To verify the employed Presage™ST2 assay established in our study laboratory for its intended use, a total number of 70 left over plasma samples obtained from septic patients which have prior been tested for sST2 with the same assay at the Department of Laboratory Medicine, Barmherzige Brueder Linz, Austria, will be retested. This cohort therefore serves as a validation cohort. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prognostic value of biomarkers in bacteremia |  | 2 years |