Preclinical Detection of Sepsis Early in Hospitalized Patients Following Surgery, Injury or Severe Illness (Pre-SEPSIS)

Preclinical Detection of Sepsis Early in Hospitalized Patients Following Surgery, Injury or Severe Illness (Pre-SEPSIS Trial)

This clinical study is to evaluate a novel biomarker - CNA Rapid Sepsis Dx - to predict the development of sepsis in patients admitted to the hospital with non-sepsis conditions. Using circulating cell-free DNA (cfDNA) in the blood stream, it has been demonstrated to detect infection response days before clinical evidence of sepsis manifests. The hypothesis is that blood biomarkers drawn daily in the hospital will identify patients who develop sepsis within seven days of hospital presentation.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Diagnostic test: CNA Rapid Sepsis Dx

Detailed Description

This is a prospective observational trial evaluating CNA Rapid Sepsis Dx -novel biomarkers (CNA Diagnostics Inc.; Calgary, Canada) based on circulating cell-free DNA (cfDNA) in the blood stream to identify patients originally admitted with non-sepsis conditions who ultimately develop sepsis according to Sepsis-3 criteria within seven days of hospital presentation. This novel technology has been demonstrated to detect host-related response to infection days before clinical evidence of sepsis manifests.

The primary objective of this study is to assess the performance of the novel diagnostic assay, CNA Rapid Sepsis Dx, based on the biomarkers, drawn daily from the day of hospital presentation, to identify patients who ultimately develop sepsis according to Sepsis-3-definition within seven days of hospital presentation.

The secondary objective is to correlate the CNA Rapid Sepsis Dx with clinically relevant outcomes such as infections that otherwise do not meet Sepsis-3 criteria, intensive care unit (ICU) length of stay, hospital length of stay, fluid culture results, and hospital mortality.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: Patrick Medado; Phone Number: 3135777500; Email: pmedado@wayne.edu
• Study Contact Backup: Name: Linda Gojcevic; Phone Number: 3135777500; Email: linda.gojcevic@wayne.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
      • Contact: Alyssa Kirkman; Phone Number: 205-934-5890; Email: akirkman@uabmc.edu
      • Principal Investigator: Jan Jansen, MBBS, PhD
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
      • Contact: Samuel Ceckowski; Phone Number: 313-966-9265; Email: sceckows@med.wayne.edu
    • Detroit, Michigan, United States, 48201
      • Detroit Receiving Hospital
      • Contact: Samuel Ceckowski; Phone Number: 313-966-9265; Email: sceckows@med.wayne.edu
      • Principal Investigator: Robert Ehrman, MD
    • Detroit, Michigan, United States, 48235
      • Sinai-Grace Hospital
      • Principal Investigator: Robert Ehrman, MD
      • Contact: Thomas Mazzocco; Phone Number: 313-966-1829; Email: tmazzocco@wayne.edu
  • New York
    • New York, New York, United States, 11042
      • Northwell Health
      • Contact: Ramona Ramdeo; Phone Number: 516-465-5400; Email: rramdeo@northwell.edu
      • Principal Investigator: Mangala Narasimhan, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to the hospital and admitted for non-sepsis conditions who are at increased risk for developing sepsis per Sepsis-3 criteria within the hospital.

Description

Inclusion Criteria:

1. Patient 18 years of age or older at the time of enrollment

2. Presence of any of the following high-risk features:

   • Victims of trauma with either an Injury Severity Score of ≥ 15 or a Glasgow Coma Score of ≤ 8[2] OR
   • Any patient undergoing high-risk surgical procedures including any emergency surgery and high risk elective surgery procedures involving the thorax, esophagus, stomach, small bowel, large bowel [3, 4] OR
   • Any patient being admitted to any ICU setting for any reason with no current evidence or suspicion of active infection (by primary team).[5, 6]
3. Able to collect sample within 24 hours of presentation to the hospital.

Exclusion Criteria:

1. Prisoners or in police custody
2. Pregnancy
3. Pre-existing infection for which patient is being treated with antibiotics as an outpatient.
4. Plan for ongoing antibiotic therapy by treating team (up to three doses antibiotics for peri-procedure prophylaxis is allowable).
5. Moribund, unlikely to survive the duration of active enrollment
6. Comfort care measures in place or ordered at time of screening OR indication from treating team that active medical care will not be pursued due to patient's condition or patient's/family's wishes.
7. Palliative care or hospice consult at time of screening.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical development of sepsis	Sepsis determined according to Sepsis-3 definition	Seven Days from hospital presentation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SIRS sepsis	Infection with systemic inflammatory response syndrome (SIRS) criteria	Seven Days from hospital presentation
Hospital Length of Stay	Duration of hospital stay in survivors and non-survivors from date/time of hospital presentation to order for discharge.	Up to 12 months
Intensive Care Unit Length of Stay	Duration of ICU stay in survivors and non-survivors from date/time of ICU admission to date/time order for transfer / discharge from ICU.	Up to 6 months
Development of non-Sepsis 3 Infections	An infection is suspected (by any degree of confidence) but the subject does not meet criteria for either Sepsis-3 or SIRS sepsis.	Seven Days from hospital presentation
Body Fluid Culture Results	All fluid culture results (blood, CSF, urine, synovial, ascitic, abscess, etc) collected during the study period will be recorded	Seven Days from hospital presentation

Collaborators and Investigators

• Sponsor: Robert Ehrman

Study record dates

Study Major Dates

• Study Start (Anticipated): December 9, 2019
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): April 30, 2021

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Biomarker; Sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: 2019R110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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