STUDY00015328: Sepsis Endotypes

Diagnostic and Prognostic Biomarkers to Elucidate Sepsis Endotypes

Determine the utility of biomarkers measured in blood and body fluid (stool, saliva, tracheal aspirate) when combined with clinical data, for predicting sepsis phenotypes that are associated with poor clinical outcomes. We hypothesize that resistin is a biomarker which provides critical prognostic information when used in conjunction with standard clinical data, in patients with sepsis and septic shock.

Study Overview

• Status: Enrolling by invitation
• Conditions: Sepsis

Detailed Description

Day 1 Sample Collection: 20ml of blood for chemical and genetic biomarker analysis. ≤1ml of saliva, stool, and tracheal aspirate for inflammatory marker analysis. Quadratus lumborum muscle size measurement and CT abdomen correlation. If not part of routine care, additional blood tests for cell differential, procalcitonin, and inflammatory markers.

Electronic Medical Records (EMR) Data: APACHE II and SOFA severity scores. Demographics, vital signs, inflammatory markers, organ dysfunction markers, and various blood chemistry values.

Days 2-3 Daily Documentation: Record the most abnormal value for the same parameters as Day 1.

Days 3-5 (Once) Sample Collection: Repeat of blood, saliva, stool, and tracheal aspirate collection. EMR data access for severity scores and other clinical parameters.

Days 5-6 Daily Documentation: Continued recording of the most abnormal values for clinical parameters.

Days 7-10 (Once) Sample Collection: Repeat of blood, saliva, stool, and tracheal aspirate collection. Measurement of muscle size and CT correlation. EMR data access for the same parameters as earlier.

Day 14 (or Discharge) Final Sample Collection: 20ml of blood and other samples, with no more than 1 ml/kg of blood collected over the entire study.

EMR and Clinical Data: Collection of severity scores, vital signs, inflammation markers, organ dysfunction markers, and other clinical variables.

Day 30, 3 Months, 6 Months, and 1 Year Long-term Outcomes: EMR review for clinical outcomes such as date of death, re-hospitalization, persistent critical illness. Phone interviews to gather subjective data about the post-hospitalization course and complications.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients in the intensive care unit (ICU) who meet critera for sepsis, as defined by the Sepsis-3 criteria and who are not excluded by any of the exclusion factors listed in the "Eligibility Criteria".

Description

Inclusion Criteria:

1. Adults (age ≥ 18 )
2. gender: male or female
3. Cognitively intact or impaired patients, given that sepsis may cause a certain degree of cognitive dysfunction in patients. All patients in the control group (no sepsis) will be cognitively intact
4. Clinical suspicion for sepsis (except for control/comparison group for whom infection is NOT a current concern)

Exclusion Criteria:

1. Patients with hematologic malignancies
2. Pregnant women
3. Patient/surrogate is not fluent in English and no translation services are available
4. Long-term immunosuppressive therapy
5. Prisoner

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Sepsis; Patients with sepsis as defined by the Sepsis-3 criteria
Control; Patients without sepsis, as defined by the Sepsis-3 criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death and chronic critical illness	The primary outcome is a composite binary variable consisting of early death and chronic critical illness which we will determine on or before day 14 after sepsis onset.	5 years for completion of study, 1 year follow up per patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The expression of BPGM and AP2 transcripts	sepsis-associated gene pathways	5 years for completion of study, 1 year follow up per patient enrolled
Clinical variables	including demographic variables (eg, age, sex, Elixhauser comorbidities), vital signs (eg, heart rate, respiratory rate, Glasgow Coma Scale score, systolic blood pressure, temperature, and oxygen saturation), markers of inflammation (eg, white blood cell count, premature neutrophil count [also called bands], erythrocyte sedimentation rate, and C-reactive protein), markers of organ dysfunction or injury (eg, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, international normalized ratio, partial pressure of oxygen, platelets, and troponin), and serum levels of glucose, sodium, hemoglobin, chloride, bicarbonate, lactate, and albumin.	5 years for completion of study, 1 year follow up per patient enrolled
Acute Physiology and Chronic Health Evaluation II Score	scale 0-71, with higher scores being worse	5 years for completion of study, 1 year follow up per patient enrolled
Sequential Organ Failure Assessment	scale of 0-24, with higher scores being worse score	5 years for completion of study, 1 year follow up per patient enrolled
Muscle measurements	Clinical measurement of quadriceps depth (ultrasound) and skeletal muscle area (on existing CT scan)	5 years for completion of study, 1 year follow up per patient enrolled

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Anthony Bonavia, M.D., Milton S. Hershey Medical Center

Publications and helpful links

General Publications

• Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis. 2012 Jun;25(3):321-7. doi: 10.1097/QCO.0b013e3283528c9b.
• Stephan F, Yang K, Tankovic J, Soussy CJ, Dhonneur G, Duvaldestin P, Brochard L, Brun-Buisson C, Harf A, Delclaux C. Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients. Crit Care Med. 2002 Feb;30(2):315-22. doi: 10.1097/00003246-200202000-00009.
• Delano MJ, Thayer T, Gabrilovich S, Kelly-Scumpia KM, Winfield RD, Scumpia PO, Cuenca AG, Warner E, Wallet SM, Wallet MA, O'Malley KA, Ramphal R, Clare-Salzer M, Efron PA, Mathews CE, Moldawer LL. Sepsis induces early alterations in innate immunity that impact mortality to secondary infection. J Immunol. 2011 Jan 1;186(1):195-202. doi: 10.4049/jimmunol.1002104. Epub 2010 Nov 24.
• Cummings CJ, Martin TR, Frevert CW, Quan JM, Wong VA, Mongovin SM, Hagen TR, Steinberg KP, Goodman RB. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. J Immunol. 1999 Feb 15;162(4):2341-6.
• Macdonald SP, Stone SF, Neil CL, van Eeden PE, Fatovich DM, Arendts G, Brown SG. Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department. PLoS One. 2014 Oct 24;9(10):e110678. doi: 10.1371/journal.pone.0110678. eCollection 2014.
• Koch A, Gressner OA, Sanson E, Tacke F, Trautwein C. Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients. Crit Care. 2009;13(3):R95. doi: 10.1186/cc7925. Epub 2009 Jun 19.
• Sunden-Cullberg J, Nystrom T, Lee ML, Mullins GE, Tokics L, Andersson J, Norrby-Teglund A, Treutiger CJ. Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock. Crit Care Med. 2007 Jun;35(6):1536-42. doi: 10.1097/01.CCM.0000266536.14736.03.
• Singbartl K, Miller L, Ruiz-Velasco V, Kellum JA. Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin. Crit Care Med. 2016 Jul;44(7):e492-501. doi: 10.1097/CCM.0000000000001472.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 7, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis
• Other Study ID Numbers: 7188

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
• product manufactured in and exported from the U.S.: No