Clinical trial NCT02934997: The Role of Dysfunctional HDL in Sepsis
Official title: The Role of Dysfunctional HDL in Community and Hospital Acquired Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Septic Shock
Keywords: sepsis
septic shock
cholesterol
high density lipoprotein
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2016-10-17
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with sepsis or septic shock presenting to both sites.

Brief summary: To determine the role of dysfunctional high density lipoprotein (Dys-HDL) in predicting or mediating progression to chronic critical illness or morbid long-term outcomes in patients being treated for community-acquired or hospital-acquired sepsis.

Detailed description: The long-term goal of this research program is to characterize the antecedents and mediators of morbid long-term outcomes in patients with sepsis. Despite successful early management, sepsis is a disease with a high incidence of chronic critical illness (CCI - intensive care unit stay ≥ 14 days with organ dysfunction) and morbid long-term outcomes (functional dependence or death at 1 year), which occur frequently in early survivors. Both the rapid identification of patients at risk for morbid outcomes and the development of novel therapies are crucial for improving outcomes after sepsis. High density lipoprotein (HDL) defends against sepsis-associated organ injury by: 1) neutralizing bacterial endotoxin, 2) modulating innate cellular immunity and preventing release of inflammatory cytokines, and 3) preventing endothelial cell activation and dysfunction. However, HDL can become dysfunctional (Dys-HDL) in the setting of inflammation, losing protective functions and becoming pro-inflammatory. Our preliminary results demonstrate that Dys-HDL is present in early sepsis and that persistent Dys-HDL elevation (first 48 hours) is associated with adverse outcomes (death, hospice or nursing home care). The overall goal of this proposal is to investigate and fully characterize the role of Dys-HDL in a diverse population of patients with both CA and HA-sepsis. The central hypothesis of this study is that structural and functional changes in HDL during sepsis are associated with the persistent presence of Dys-HDL as well as the inflammation and endothelial dysfunction that lead to acute organ dysfunction, CCI, and morbid long-term outcomes. To test this, we will enroll 160 patients in a two-site, prospective, longitudinal, cohort study.

Eligibility criteria: Inclusion Criteria:

* patients meeting the recently updated definition of sepsis (suspected or confirmed infection plus ≥ 2 SOFA points) OR septic shock (hypotension not responsive to 30 mL/kg IV fluids, vasopressor requirement, and lactate ≥ 2)23 and being treated with an institutional, evidence-based guideline (EBG) management bundle for sepsis within 24 hours which has been adopted at both sites.

Exclusion Criteria:

* significant traumatic brain injury (evidence of neurologic injury on CT scan and a GCS \<8)
* refractory shock (likely death within 12 hours)
* alternative/confounding diagnosis causing shock (e.g., myocardial infarction or pulmonary embolus)
* uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)
* patients deemed futile care or have advanced directives limiting resuscitative efforts
* severe CHF (NY Heart Association Class IV)
* Child-Pugh Class B or C liver disease
* HIV/AIDS causing severe immunocompromise
* organ transplant recipient on immunosuppressive agents
* known pregnancy
* inability to obtain informed consent
* diagnosed disorders of lipid metabolism.

Primary outcomes:
measure: Early sepsis-associated organ dysfunction, incidence of chronic critical illness and morbid long-term outcomes after sepsis.
timeFrame: 1 year
Secondary outcomes:
measure: The temporal relationship between Dys-HDL and sepsis and endothelial biomarkers in patients with sepsis.
timeFrame: 4 days
measure: Explore changes in HDL function from patients with sepsis with rapid recovery versus patients with sepsis who develop CCI versus healthy controls.
timeFrame: 90 days
Other outcomes:
Locations:
Study officials:
affiliation: University of Florida
name: Faheem Guirgis, MD
role: PRINCIPAL_INVESTIGATOR
References: