LIPIDS-P Trial Phase I/II

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.

Inclusion Criteria:

1. age > 18,

2. primary diagnosis of sepsis and within 24 hours of sepsis recognition and treated with
institutional sepsis algorithm,

3. SOFA score ≥ 4,

4. screening total cholesterol ≤ 100 mg/dL or (HDL-C + LDL-C ≤ 70 mg/dL)

Exclusion Criteria:

1. total bilirubin > 2 mg/dL,

2. serum albumin < 1.5 mg/dL,

3. hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active
ingredients or excipients,

4. severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides
> 400 mg/dL,

5. alternative/confounding diagnosis causing shock or critical illness (e.g., myocardial
infarction or pulmonary embolus, massive hemorrhage, trauma),

6. significant traumatic brain injury (evidence of neurologic injury on CT scan and a GCS
<8),

7. refractory shock (likely death within 12 hours),

8. established Do Not Resuscitate status or advanced directives restricting aggressive
care or treating physician deems aggressive care unsuitable,

9. anticipated requirement for surgery that would interfere with drug infusion,

10. severe primary blood coagulation disorder,

11. acute pancreatitis accompanied by hyperlipidemia,

12. acute thromboembolic disease,

13. uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable
dead bowel),

14. severe immunocompromised state (e.g. subject has neutropenia receiving cytotoxic
chemotherapy with absolute neutrophil count < 500/ul or expected to decline to <
500/uL within the next 3 days),

15. pregnancy or lactation

16. already receiving intravenous lipid formulations (e.g., TPN, propofol) will be
excluded from the study as lipid infusion will interfere with interpretation of the
study results.

17. Child Pugh Class B/C liver disease patients