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Genotypes and Phenotypes in Pediatric SIRS and Sepsis (GAPPSS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02728401
Recruitment Status : Completed
First Posted : April 5, 2016
Last Update Posted : April 19, 2018
Sponsor:
Collaborator:
Immunexpress
Information provided by (Responsible Party):
Jerry Zimmerman, Seattle Children's Hospital

Tracking Information
First Submitted Date March 30, 2016
First Posted Date April 5, 2016
Last Update Posted Date April 19, 2018
Actual Study Start Date May 1, 2013
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 30, 2016)
Gene Expression Levels [ Time Frame: Day 1 of admission to the pediatric intensive care unit (PICU) ]
Gene expression levels (quantitative) will be compared between CSSS, INSI and viral infection groups, in a search for signatures that can discriminate these groups
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: March 30, 2016)
Serum Protein Expression Profiles [ Time Frame: Day 1 of admission to the pediatric intensive care unit (PICU) ]
Serum protein expression profiles (semi-quantitative) will be compared between CSSS and INSI groups, in a search for signatures that can discriminate the two groups
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genotypes and Phenotypes in Pediatric SIRS and Sepsis
Official Title Genotypes and Phenotypes in Pediatric SIRS and Sepsis (GAPPSS)
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.
Detailed Description

The investigators will undertake a proof-of-concept, pilot, prospective, observational trial that aims to recruit ~90 children from the Seattle Children's Hospital Pediatric Intensive Care Unit (PICU) and Cardiac Intensive Care Unit (CICU). The study will plan to recruit 30 children who are scheduled for surgery to repair congenital cardiac malformations, 15 - 25 immunocompetent children with culture positive sepsis, and 15 - 25 immunocompromised children with culture positive sepsis, and 30-40 children who are polymerase chain reaction (PCR) positive for viral respiratory pathogens (RSV, influenza, parainfluenza, rhinovirus, etc), and who meet the eligibility criteria. In total, accounting for culture negative bacterial sepsis (estimated 40%), the investigators plan to enroll 50 children with sepsis, 30-40 with viral sepsis, and 20 children undergoing surgery for congenital heart disease.

Demographic data will be collected at the time of ICU admission. Illness severity will be quantified by PRISM III and day 1 PELOD scores. Additional measures of sepsis severity will include oxygenation index, saturation index and duration of mechanical ventilation, vasoactive inotropic score and duration of vasoactive-inotropic support and highest serum creatinine on day 1. Resource utilization will be measured as PICU and hospital duration of stay.

For all children enrolled in the study, blood samples will be obtained on study days 1, 2 and 3. For children with sepsis, if cultures remain sterile or PCR negative, no additional research blood samples will be obtained. For children with sepsis and a positive culture or positive PCR by study day 3, additional blood samples will be obtained on the day of PICU discharge.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
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).
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.

Condition
  • Systemic Inflammatory Response Syndrome (SIRS)
  • Sepsis
Intervention Not Provided
Study Groups/Cohorts
  • 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).
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: April 17, 2018)
104
Original Estimated Enrollment
 (submitted: March 30, 2016)
90
Actual Study Completion Date December 31, 2017
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

A. INSI group: systemic inflammation, in the absence of culture positive infection. Cardiac surgery patients, n=30.

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • PICU nosocomial primary infection accounting for the sepsis event
  • Not expected to survive the PICU stay
  • Ward of the state

C. Viral Infection group. Severe respiratory dysfunction in the presence of PCR -documented viral infection. Children with clinical severe viral sepsis, n=6. In this group, the investigators will enroll children who are immunocompetent as well as children who are immunocompromised.

Inclusion Criteria:

  • 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
  • Parents speak English AND
  • Severe respiratory dysfunction requiring invasive or non-invasive positive pressure mechanical ventilation support AND
  • Positive PCR verifying a viral infection
  • Not previously enrolled in the GAPPSS investigation

Exclusion Criteria:

  • PICU nosocomial primary infection accounting for the sepsis event
  • Not expected to survive the PICU stay
  • Ward of the state
Sex/Gender
Sexes Eligible for Study: All
Ages 38 Weeks to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02728401
Other Study ID Numbers 14761
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: The investigators plan to publish the results of the GAPPSS study in a peer-reviewed scientific journal. A supplemental digital file associated with this paper will be made publicly available through a web link, and will contain relevant clinical data (with all patients de-identified).
Responsible Party Jerry Zimmerman, Seattle Children's Hospital
Study Sponsor Seattle Children's Hospital
Collaborators Immunexpress
Investigators
Principal Investigator: Jerry J Zimmerman, MD, PhD Seattle Children's Hospital
PRS Account Seattle Children's Hospital
Verification Date April 2018