LIPIDS-P Trial Phase I/II Trial

Phase 1

Completed

• Conditions: Sepsis, Severe; Septic Shock
• Interventions: Drug: Smoflipid

• Registration Number: NCT03405870
• Lead Sponsor: University of Florida

Brief Summary

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).

Detailed Description

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 Timeline

• Study First Submitted: 2018-01-12
• Study First Submitted QC: 2018-01-12
• Study First Posted: 2018-01-23
• Study Start: 2018-08-17
• Primary Completion: 2023-04-26
• Study Completion: 2023-04-26
• Results First Submitted: 2023-06-16
• Status Verified: 2025-02
• Results First Submitted QC: 2025-07-23
• Last Update Submitted: 2025-07-23
• Results First Posted: 2025-08-11
• Last Update Posted: 2025-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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 or liver transplant recipient
18. Patients on, or anticipated to be placed on, ECMO within 48 hours of enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase II - 1.2 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase II - 1.4 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase II - 1.6 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase I - 1.0 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase I - 1.2 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase I - 1.4 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.
Phase I - 1.6 g/kg Smoflipid	Smoflipid	Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Primary Outcome Measures

Name	Time	Method
Phase II - Primary Outcome - Change in Total Cholesterol (48 Hours - Enrollment)	48 hours	Change in total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL
Phase I - Primary Outcome - Maximum Tolerated Dose/Participants Experiencing Dose Related Toxicity	First 48 hours	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.

Secondary Outcome Measures

Name	Time	Method
Phase II - Secondary Outcome - Organ Dysfunction	48 hours	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.

Trial Locations

Locations (3)

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