POC SPLA2-IIA as a Biomarker for Sepsis and Septic Shock

Bedside Measurements of a Novel Biomarker SPLA2-IIA as a Marker of an Inflammatory Response and Predictor of Sepsis in Patients Meeting SIRS or qSOFA Criteria: a Pilot Study

Septic shock is a major cause of morbidity and mortality. SIRS (systemic inflammatory response syndrome) can progress over hours to days to severe sepsis and septic shock. Currently, lactate levels are used to guide resuscitative efforts and have been shown to be a predictor of mortality independent of vital sign abnormalities (1). However, their use seems to be limited to trending in a given patient, and not for prognostic value of a single level (2). This is because there is significant overlap in lactate levels of individuals who progress to death and multisystem organ failure as compared to those who do not (2). Blood cultures are also extensively used to detect blood stream infection (BSI), but these are time consuming and are not immediately useful to clinicians caring for sick patients.

A biomarker that adequately distinguishes between patients at high risk for progression to severe sepsis/shock/death and those who will not would be helpful in the appropriate initiation of aggressive treatment and appropriate disposition of patients in clinical care. Previously, the investigators demonstrated that sPLA2-IIA detected by ELISA assay had a sensitivity of 87% and a specificity of 91% in detecting sepsis (3). Zeus Pharmaceuticals has developed a bedside point-of-care test measuring sPLA2-IIA in real time. The investigators propose to study this assay in terms of its discriminatory value in distinguishing between SIRS from non-infectious causes, sepsis, severe sepsis, and septic shock in a cohort of patients presenting to the emergency department at Anderson and Bethlehem campuses. The investigators propose to better define the threshold level for this marker assay as well as seek to establish its utility in a clinical population.

The investigators will take samples of blood from emergency department patients presenting who meet SIRS criteria or have a positive q-SOFA screen. The investigators will take subsequent samples of blood when lactate levels are redrawn as per St. Luke's sepsis protocol. After informed consent is obtained, blood specimens will be run in analyzer provided by Zeus for sPLA2-IIA. The investigators will record presence and quantity of sPLA2-IIA, as well as other markers of sepsis such as lactate, vital signs, blood cultures, and patient oriented outcomes (ie ICU days, organ dysfunction, and survival to discharge). Printouts from analyzer will be stored in locked cabinet, and remaining blood will be discarded. The data will then be compiled by the investigators at St. Luke's University Hospital. The results will be correlated with the patients' clinical progression to determine the biomarker's utility and cut-off values for predicting progression of SIRS.

As clear threshold levels for this marker have yet to be defined, the investigators would like to enroll patients meeting criteria until the investigators have enrolled 50 patients with septic shock. It is anticipated that, proportionally, this will lead to enrollment of 75-100 patients with severe sepsis, 100-150 patients with sepsis, and 100-150 patients meeting SIRS criteria who are not septic. This will help delineate if there is any value in this assay for distinguishing among the severity of sepsis pathophysiology.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Diagnostic test: SPLA2-IIA

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Recruiting
      • St. Luke's University Health network
      • Contact: Rebecca Jeanmonod, MD; Phone Number: 610-838-6147; Email: rebeccajeanmonod@yahoo.com
      • Contact: Donald Jeanmonod, MD; Phone Number: 610 500 3733; Email: jeanmono@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

emergency department patients with positive sepsis screens

Description

Inclusion Criteria:

• presenting to emergency department with positive sepsis screen including 2 SIRS criteria or positive q-sofa score regardless of reasons for positive screen

Exclusion Criteria:

• inability to consent or to have surrogate consent, identification after resuscitation or after blood has already been drawn, age less than 18, pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
septic shock	Diagnostic test: SPLA2-IIA; bedside blood test
severe sepsis	Diagnostic test: SPLA2-IIA; bedside blood test
sepsis	Diagnostic test: SPLA2-IIA; bedside blood test
sirs positive, not septic	Diagnostic test: SPLA2-IIA; bedside blood test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level greater than 25ng	threshold level of spla2-IIA	baseline
level greater than 25ng	threshold level of spla2-IIA	2 hours
level greater than 25ng	threshold level of spla2-IIA	24 hour lab draw

Collaborators and Investigators

• Sponsor: St. Luke's Hospital, Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2019
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: SLIR 2019-23

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