Genotypes and Phenotypes in Pediatric SIRS and Sepsis

NCT02728401 | Completed

• 1 other identifier: 14761
• Study Type: observational
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this investigation is to longitudinally quantify host gene expression and serum proteins in children with infectious and non-infectious SIRS. The investigators hypothesize that children with non-infectious SIRS, with bacterial infection associated SIRS, or with viral infection associated SIRS will exhibit distinct patterns of host gene expression and serum proteins. The investigators further hypothesize that it should be possible to discover sets of mRNA or protein biomarkers that will permit unambiguous diagnosis of non-infectious SIRS, SIRS associated with bacterial infection, and SIRS associated with viral infection.

Conditions

Systemic Inflammatory Response Syndrome (SIRS); Sepsis

Keywords

inflammation; sepsis; pediatric; transcripts; serum proteins; cardiopulmonary bypass

Outcome Measures

Primary Outcomes (1)

• Gene Expression Levels

  Gene expression levels (quantitative) will be compared between CSSS, INSI and viral infection groups, in a search for signatures that can discriminate these groups

  Day 1 of admission to the pediatric intensive care unit (PICU)

Secondary Outcomes (1)

• Serum Protein Expression Profiles

  Day 1 of admission to the pediatric intensive care unit (PICU)

Study Arms (3)

INSI

Infection-negative systemic inflammation (INSI). The INSI group consists of children who have undergone congenital cardiac defect corrective surgery requiring cardiopulmonary bypass, known to induce an INSI response for \~24 hours thereafter; all children in this cohort are culture negative. This group is demarcated further by inclusion \& exclusion criteria (see Eligibility section below).

CSSS

Clinical severe sepsis syndrome (CSSS). Children assigned to the CSSS group had confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), exhibited 2 or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and demonstrated at least cardiovascular ± pulmonary organ dysfunction. This group is demarcated further by inclusion \& exclusion criteria (see Eligibility section below).

Viral

The Viral Infection group consists of children who displayed signs and symptoms of severe viral infection, and who tested positive for respiratory viral infection(s) by a molecular virus panel test. These children were clinically evaluated to not have bacterial sepsis. This group is demarcated further by inclusion \& exclusion criteria (see Eligibility section below).

Eligibility Criteria

• Age: 38 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

INSI group: children who had congenital cardiac defect corrective surgery requiring cardiopulmonary bypass, known to induce an INSI response for \~24 hours thereafter. All children in this group were immune competent and culture negative. CSSS group: children with confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), SIRS criteria (including fever/hypothermia and leukocytosis/leukopenia), and at least cardiovascular ± pulmonary organ dysfunction. Viral Infection group: children with severe respiratory dysfunction in the presence of PCR -documented viral infection.

You may qualify if:

• Admission to the CICU AND
• Age \~1-18 years AND
• Weight exceeding 10 kg
• Vascular catheter capable of providing the blood draw or anticipated orders for venipuncture for clinical labs AND
• Status post open heart surgery requiring cardiopulmonary bypass AND
• Parents speak English AND
• Not previously enrolled in the GAPPSS investigation

You may not qualify if:

• Pre- or post-operative culture positive infection OR
• Not expected to survive the CICU stay OR
• Ward of the state OR
• Concurrent malignancy or autoimmune disorder
• B. CSSS (Clinical Severe Sepsis Syndrome) group: systemic inflammation, in the presence of highly suspected or documented bacterial infection. Children with clinical severe sepsis, n = 40. In this group, the investigators will enroll children who are immunocompetent as well as children who are immunocompromised.
• Admitted to the PICU AND
• Age newborn (\>38 weeks EGA)-18 years AND
• Weight equal to or greater than 4 kg AND
• Vascular catheter capable of providing the blood draw or anticipated orders for venipuncture for clinical labs AND
• At least one organ dysfunction (severe sepsis) AND
• Parents speak English AND
• SIRS (systemic inflammatory response syndrome) AND
• Strongly suspected or documented source of infection
• Not previously enrolled in the GAPPSS investigation
• PICU nosocomial primary infection accounting for the sepsis event

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Immunexpress: collaborator

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (4)

• Mathias B, Mira JC, Larson SD. Pediatric sepsis. Curr Opin Pediatr. 2016 Jun;28(3):380-7. doi: 10.1097/MOP.0000000000000337.

  PMID: 26983000 BACKGROUND

• Weiss SL, Fitzgerald JC, Pappachan J, Wheeler D, Jaramillo-Bustamante JC, Salloo A, Singhi SC, Erickson S, Roy JA, Bush JL, Nadkarni VM, Thomas NJ; Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015 May 15;191(10):1147-57. doi: 10.1164/rccm.201412-2323OC.

  PMID: 25734408 BACKGROUND

• Zimmerman JJ, Sullivan E, Yager TD, Cheng C, Permut L, Cermelli S, McHugh L, Sampson D, Seldon T, Brandon RB, Brandon RA. Diagnostic Accuracy of a Host Gene Expression Signature That Discriminates Clinical Severe Sepsis Syndrome and Infection-Negative Systemic Inflammation Among Critically Ill Children. Crit Care Med. 2017 Apr;45(4):e418-e425. doi: 10.1097/CCM.0000000000002100.

  PMID: 27655322 RESULT

• McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ, Presneill JJ, Venter DJ, Lipman J, Thomas MR, Klein Klouwenberg PM, van Vught L, Scicluna B, Bonten M, Cremer OL, Schultz MJ, van der Poll T, Yager TD, Brandon RB. A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts. PLoS Med. 2015 Dec 8;12(12):e1001916. doi: 10.1371/journal.pmed.1001916. eCollection 2015 Dec.

  PMID: 26645559 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Type 1: whole blood (2.5 mL) collected daily into PAXgene Blood RNA tube (PreAnalytiX, Ref # 7621650). Type 2: whole blood (1 mL) collected daily into serum separation tube (BD Vacutainer SST™ Tube with Silica Clot Activator, Polymer Gel, Silicone-Coated Interior, Ref # 367983). Type 3: whole blood (1 mL) collected on day 1 into lavender top Vacutainer (BD Vacutainer, lavender top, K2 EDTA 7.2mg, Ref # 367861).

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Sepsis; Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Infections

Study Officials

• Jerry J Zimmerman, MD, PhD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Anesthesiology, Faculty in Pediatric Critical Care Medicine, University of Washington School of Medicine

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: May 1, 2013
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: April 19, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)