Investigating immune responses in surgical sepsis patients

Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology Subtitle: Pathological Myeloid Activation After Sepsis and Trauma

This study is trying to understand how certain immune cells behave in patients with surgical sepsis to see if it affects their recovery and risk of infections later on.

Quick facts

• Study type: Observational
• Enrollment: 450 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: University of Florida (other)
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT05110937 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the mechanisms behind dysfunctional myelopoiesis and the expansion of myeloid-derived suppressor cells (MDSCs) in patients with surgical sepsis. By following these patients over time, the study will assess how MDSC populations evolve and their impact on long-term clinical outcomes, including the risk of secondary infections. The research will focus on identifying epigenetic changes in MDSCs and their role in driving immune suppression and inflammation following sepsis. The findings could provide insights into potential therapeutic targets for improving recovery in sepsis patients.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who meet the Sepsis-3 criteria for sepsis or septic shock.

Not a fit: Patients with significant immune dysfunction, advanced comorbidities, or those who are not expected to recover from sepsis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management strategies for patients recovering from surgical sepsis, potentially reducing complications and enhancing quality of life.

How similar studies have performed: While the specific approach of this study is novel, previous research has indicated that understanding immune responses in sepsis can lead to better outcomes, suggesting potential for success.

Eligibility criteria

Sepsis participant:

Inclusion Criteria:

1. age ≥18 years
2. meets criteria for sepsis/septic shock by Sepsis-3 consensus criteria.

Exclusion Criteria:

1. have disease states that predispose to significant immune system dysfunction
2. have comorbidity burden or goals of care that preclude recovery after sepsis. These criteria include:

   a. irreversible shock (death \<12 hours) b. uncontrollable surgical source of sepsis c. patients deemed to be futile care or have advanced directives limiting resuscitative efforts d. alternative diagnoses causing shock state (e.g., hemorrhage, myocardial infarction or pulmonary embolus) e. known HIV infection with CD4+ count \<200 cells/mm3 g. severe traumatic brain injury with unencumbered assessment of GCS equaling 3 on admission to the intensive care unit.
3. known pregnancy
4. enrollment \>96 hours after suspected sepsis onset
5. pre-hospitalization bedridden performance status (WHO/Zubrod score ≥4)
6. subsequent clinical adjudication diagnosis not consistent with sepsis/septic shock by Sepsis-3 criteria.
7. Burn injury greater than 20% total body surface area (tBSA)

Trauma Participant:

Inclusion Criteria

1. All adults age ≥ 18 years
2. Blunt trauma patient with a. Injury Severity Score (ISS) greater than or equal to 25 b. ISS \> 15 and one of the following: i. \> 4 units of PRBC or \>3 units of whole blood or \>1500 ml of autogenous blood product in the first 24 hours of admission ii. AIS (acute injury score) \> 2 spine iii. Shock on arrival (Systolic blood pressure (SBP) \< 90)

OR

c. ISS \> 15 and two of the following: i. Age \> 55 ii. AIS \> 2 chest iii. +ETOH (ethyl alcohol) on arrival iv. Any red blood cell transfusion in first 24 hours

Exclusion Criteria

1. Patients not expected to survive greater than 48 hours.
2. Prisoners.
3. Pregnancy.
4. Previous bone marrow transplantation.
5. Patients with End Stage Renal Disease.
6. Patients with any pre-existing hematological disease.
7. Patients deemed to be futile care or have advanced directives limiting resuscitative efforts.
8. Known HIV infection with CD4+ count \<200 cells/mm3
9. Burn injury greater than 20% tBSA

Where this trial is running

Gainesville, Florida

• UF Health at Shands hospital — Gainesville, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Lyle Moldawer, PhD — University of Florida
• Study coordinator: Jennifer Lanz, MSN

Conditions: Sepsis, Trauma Injury