The Role of Dysfunctional HDL in Sepsis

Sepsis Clinical Trial

Official title:

The Role of Dysfunctional HDL in Community and Hospital Acquired Sepsis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02934997
• Other study ID #: IRB201701349-N
• Secondary ID: UFlorida1K23GM11
• Status: Completed
• Start date: November 1, 2016
• Est. completion date: May 3, 2019

Study information

• Verified date: February 2020
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: May 3, 2019
• Est. primary completion date: May 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Shock, Septic
• Toxemia

Intervention

Other:
• Observational study

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	National Institute of General Medical Sciences (NIGMS)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early sepsis-associated organ dysfunction, incidence of chronic critical illness and morbid long-term outcomes after sepsis.		1 year
Secondary	The temporal relationship between Dys-HDL and sepsis and endothelial biomarkers in patients with sepsis.		4 days
Secondary	Explore changes in HDL function from patients with sepsis with rapid recovery versus patients with sepsis who develop CCI versus healthy controls.		90 days