LIPIDS-P Trial Phase I/II

Septic Shock Clinical Trial

— LIPIDS-P  

Official title:

The LIPid Intensive Drug Therapy for Sepsis ¬Pilot (LIPIDS-P) Phase I/II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03405870
• Other study ID #: IRB201800027 - A
• Secondary ID: OCR19642
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 17, 2018
• Est. completion date: December 1, 2022

Study information

• Verified date: January 2022
• Source: University of Florida
• Contact: Faheem W Guirgis, MD
• Phone: 904-244-4986
• Email: faheem.guirgis[@]jax.ufl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Sepsis, Severe
• Septic Shock

Intervention

Drug:
• Smoflipid
Administration of lipid injectable emulsion

Locations

Country	Name	City	State
United States	Department of Emergency Medicine, UF Health Jax ICU/MICU	Jacksonville	Florida
United States	UF Health Jacksonville	Jacksonville	Florida
United States	UF Health Jacksonville North campus	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Cholesterol	Delta total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL	48 hours
Primary	Maximum Tolerated Dose	Evaluate for dose limiting toxicities for the Phase I study	First 7 days
Secondary	Lipid Oxidation	HDL inflammatory index (ranges from 0-10)	48 hours
Secondary	HDL function	Cholesterol efflux, this is a percentage from 0-100%	48 hours
Secondary	Organ Dysfunction	Sequential Organ Failure Assessment (SOFA) Score, this is a numerical score ranging from 0 to 24	48 hours, 7 days
Secondary	Mortality	Mortality	In-hospital, 28 day