Briefly, this pilot clinical trial will evaluate preliminary safety and efficacy of the study drug (Smoflipid) at elevating cholesterol levels (primary outcome) in patients with sepsis and moderate organ dysfunction and will also evaluate measures of organ dysfunction, mortality, and biological activity (secondary outcomes).
Sepsis is a life-threatening disease for which there are no effective treatments. It results from metabolic and immunologic derangements that lead to organ dysfunction, shock and sometimes death. Both "good" (high density lipoprotein, HDL) and "bad" (low density lipoprotein, LDL) cholesterol should be protective against sepsis by helping to clear bacterial toxins from the blood stream and by providing a fuel for endogenous corticosteroids, part of the body's protective stress-response in shock. However, for partially unknown reasons, cholesterol levels drop to critically low levels in early sepsis, leaving the body unable to protect itself against sepsis via these mechanisms. Currently, lipid emulsions are available that are FDA approved for intravenous nutrition in critically ill patients (including sepsis) and may be capable of elevating serum cholesterol levels. This Phase II randomized pilot clinical trial, proposes to assess the following in a cohort of patients with early sepsis (first 24 hours): 1) safety and tolerability of the proposed lipid injectable emulsion (Smoflipid) and any adverse effects, 2) the drugs ability to optimally elevate cholesterol at 48 hours, and 3) preliminary measures of biological activity and clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
59
Administration of lipid injectable emulsion
Department of Emergency Medicine, UF Health
Gainesville, Florida, United States
UF Health Emergency Medicine
Gainesville, Florida, United States
UF Health Jacksonville North campus
Jacksonville, Florida, United States
Phase II - Primary Outcome - Change in Total Cholesterol (48 Hours - Enrollment)
Change in total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL
Time frame: 48 hours
Phase I - Primary Outcome - Maximum Tolerated Dose/Participants Experiencing Dose Related Toxicity
Using sequential dose escalation, participants received 2 doses of 1.0 to 1.6 g/kg of lipid emulsion (Smoflipid 20% lipid emulsion) within 48 hours of enrollment to test the maximum tolerated dose of study drug. The maximum tolerated dose was defined by patients exhibiting specific dose-related toxicities from administration of escalating doses of the study drug. Of 9 patients, adverse events were only considered dose-limiting toxicities if they met the predefined study protocol criteria. None of these were classified as dose limiting or serious.
Time frame: First 48 hours
Phase II - Secondary Outcome - Organ Dysfunction
Sequential Organ Failure Assessment (SOFA) Score, this is a numerical score ranging from 0 to 24. A Higher SOFA score represents worsening organ dysfunction is correlated with higher rate of mortality. We measured the change over 48 hours.
Time frame: 48 hours
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