Clinical trial NCT01359891: Clinical Evaluation of Novel Biomarkers in Patients With Septicemia
Official title: Clinical Evaluation of Novel Biomarkers for Diagnosis, Therapy- Monitoring and Prognosis of Outcome in Patients With Septicemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Bacteremia
Fungemia
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2011-05-25
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients \>18years with suspected / proven bacteremia/septicaemia admitted to the medical university hospital Graz, Austria

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Patients above 18 years

Exclusion Criteria:

* Patients \< 18 years

Primary outcomes:
measure: prognostic value of biomarkers in bacteremia
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University Hospital of Graz
state: Styria
Study officials:
affiliation: Medical University of Graz
name: Martin Hoenigl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Graz
name: Robert Krause, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University Hospital Graz
name: Reinhard R Raggam, MD
role: PRINCIPAL_INVESTIGATOR
References: