Early Identification of Sepsis in Children

This observational nation-wide study is focused on evaluation of the new possible biomarkers for pediatric sepsis and their specificity/sensitivity in combination with usual diagnostic markers for sepsis in the terms of early identification of sepsis, severe sepsis, and septic shock.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Shock, Septic; SIRS; Sepsis, Severe
• Intervention / Treatment: Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin

Detailed Description

The understanding of sepsis pathophysiology underwent a great progress during the last decades and the therapy of sepsis is in the focus of the research for many years, but sepsis is still one of the main causes of death in the ICUs around the world. Systemic inflammatory response syndrome (SIRS) is closely connected with the sepsis development, but SIRS also represents a high risk of organ dysfunction in non-infectious patients (trauma, stress, cardiopulmonary arrest). Early diagnosis and prevention of the organ dysfunction are the mainstay of the correct and timely therapy, but currently there is no reliable, quick and simple method for the diagnosis of sepsis. And also there is no generally accepted clinical or laboratory parameter, which can be used to differentiate between sepsis and SIRS.

There are some commonly available biomarkers that showed promising results in critically ill adult patients. Those include immature platelet fraction (IPF), immature granulocytes (IG) count and nucleated red blood cells (NRBC) count. The knowledge of their variability in different phases of illness (SIRS/sepsis/severe sepsis/septic shock) in pediatric patients is very limited, as is their connection with other generally used markers of infection (CRP, procalcitonin, presepsin).

This study is strictly non-interventional and focused on usability of above mentioned biomarkers in the early diagnosis of sepsis/SIRS and on the reduction of morbidity/mortality of pediatric intensive care unit (PICU) patients with sepsis/SIRS.

In all patients admitted to PICU in selected study period, the inflammation markers - C-reactive protein (CRP), procalcitonin (PCT), presepsin (soluble cluster of differentiation 14-subtypes) and full blood count parameters -IPF,IG,NRBC will be measured at the time of admission and on 3rd, 5th and 7th day of stay in intensive care. The organ dysfunction score will be evaluated daily.

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

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 61300
    • Recruiting
    • University Hospital Brno
    • Contact: Michal Fedora, MD., Ph.D.; Phone Number: +420532234698; Email: fedora.michal@fnbrno.cz
    • Contact: Jozef Klučka, MD.; Phone Number: +420532234696; Email: klucka.jozef@fnbrno.cz
    • Principal Investigator: Petr Dominik, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children admitted to PICU.

Description

Inclusion Criteria:

• all patients admitted to PICU until the 18th year of age
• expected length of stay > 48 hours

Exclusion Criteria:

• oncology patients
• immunosuppressive therapy
• immunostimulant therapy
• autoimmune disease
• post-organ transplant patient
• thrombocytopaenia, thrombocytopathy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No SIRS; Children without clinical signs of SIRS, according to Goldstein criteria.	Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin; Assessment of blood cell count parameters and inflammation markers - IG, IPF, NRBC, CRP, PCT, presepsin according to study group.
SIRS; Children with clinical signs of SIRS, according to Goldstein criteria.	Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin; Assessment of blood cell count parameters and inflammation markers - IG, IPF, NRBC, CRP, PCT, presepsin according to study group.
Sepsis; Children with clinical signs of sepsis, according to Goldstein criteria.	Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin; Assessment of blood cell count parameters and inflammation markers - IG, IPF, NRBC, CRP, PCT, presepsin according to study group.
Severe sepsis; Children with clinical signs of severe sepsis, according to Goldstein criteria.	Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin; Assessment of blood cell count parameters and inflammation markers - IG, IPF, NRBC, CRP, PCT, presepsin according to study group.
Septic Shock; Children with clinical signs of septic shock, according to Goldstein criteria.	Diagnostic test: IG, IPF, NRBC, CRP, PCT, presepsin; Assessment of blood cell count parameters and inflammation markers - IG, IPF, NRBC, CRP, PCT, presepsin according to study group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IG and IPF concentration for early sepsis identification	The levels of IG and IPF will be obtained in first 7 days after admission. The IG and IPF will be evaluated for the possibility of early sepsis recognition.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IG serum levels in patients with SIRS and sepsis/severe sepsis/septic shock	The levels of IG will be obtained in first 7 days after admission. The IG will be evaluated for the possibility of distinguish patients with or without SIRS and sepsis/severe sepsis/septic shock sepsis/septic shock.	7 days
IPF serum levels in patients with SIRS and sepsis/severe sepsis/septic shock	The levels of IPF will be obtained in first 7 days after admission. The IPF will be evaluated for the possibility of distinguish patients with or without SIRS and sepsis/severe sepsis/septic shock sepsis/septic shock.	7 days
NRBC cell count and critically ill patient´s outcome	The NRBC count will be obtained in first 7 days after admission. The NRBC count will be evaluated for the possibility correlation with the outcome (mortality and morbidity) of critically ill paediatric patients in PICU sepsis/septic shock?	7 days

Collaborators and Investigators

• Sponsor: Brno University Hospital
• Investigators: Principal Investigator: Petr Dominik, MD., University Hospital Brno

Publications and helpful links

General Publications

• Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6.
• De Blasi RA, Cardelli P, Costante A, Sandri M, Mercieri M, Arcioni R. Immature platelet fraction in predicting sepsis in critically ill patients. Intensive Care Med. 2013 Apr;39(4):636-43. doi: 10.1007/s00134-012-2725-7. Epub 2012 Oct 24.
• Nierhaus A, Klatte S, Linssen J, Eismann NM, Wichmann D, Hedke J, Braune SA, Kluge S. Revisiting the white blood cell count: immature granulocytes count as a diagnostic marker to discriminate between SIRS and sepsis--a prospective, observational study. BMC Immunol. 2013 Feb 12;14:8. doi: 10.1186/1471-2172-14-8.
• Liu Y, Hou JH, Li Q, Chen KJ, Wang SN, Wang JM. Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: a systematic review and meta-analysis. Springerplus. 2016 Dec 12;5(1):2091. doi: 10.1186/s40064-016-3591-5. eCollection 2016.
• Enz Hubert RM, Rodrigues MV, Andreguetto BD, Santos TM, de Fatima Pereira Gilberti M, de Castro V, Annichino-Bizzacchi JM, Dragosavac D, Carvalho-Filho MA, De Paula EV. Association of the immature platelet fraction with sepsis diagnosis and severity. Sci Rep. 2015 Jan 26;5:8019. doi: 10.1038/srep08019.
• Schaer C, Schmugge M, Frey B. Prognostic value of nucleated red blood cells in critically ill children. Swiss Med Wkly. 2014 Mar 28;144:w13944. doi: 10.4414/smw.2014.13944. eCollection 2014.
• Straney L, Clements A, Parslow RC, Pearson G, Shann F, Alexander J, Slater A; ANZICS Paediatric Study Group and the Paediatric Intensive Care Audit Network. Paediatric index of mortality 3: an updated model for predicting mortality in pediatric intensive care*. Pediatr Crit Care Med. 2013 Sep;14(7):673-81. doi: 10.1097/PCC.0b013e31829760cf.
• Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F; Groupe Francophone de Reanimation et d'Urgences Pediatriques (GFRUP). PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit Care Med. 2013 Jul;41(7):1761-73. doi: 10.1097/CCM.0b013e31828a2bbd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: March 15, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 2, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: septic shock; children; sepsis; SIRS; severe sepsis; immature platelet fraction (IPF); immature granulocytes (IG); nucleated red blood cells (NRBC)
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Toxemia; Shock, Septic
• Other Study ID Numbers: FNBRNO-2017/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No