LIPIDS-P Trial Phase I/II (LIPIDS-P)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Sepsis, Severe
• Intervention / Treatment: Drug: Smoflipid

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 Type: Interventional
• Enrollment (Anticipated): 68
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Faheem W Guirgis, MD; Phone Number: 904-244-4986; Email: Faheem.Guirgis@jax.ufl.edu
• Study Contact Backup: Name: Morgan Henson, MPH; Phone Number: 904-244-4234; Email: Morgan.Henson@jax.ufl.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • Uf Health Jacksonville
      • Contact: Morgan Henson, MPH; Phone Number: 904-244-4234; Email: Morgan.Henson@jax.ufl.edu
      • Contact: Faheem Guirgis, MD; Phone Number: 904-244-4986; Email: Faheem.Guirgis@jax.ufl.edu
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • Department of Emergency Medicine, UF Health Jax ICU/MICU
      • Contact: Morgan Henson, MPH; Phone Number: 904-244-4234; Email: Morgan.Henson@jax.ufl.edu
      • Contact: Faheem Guirgis, MD; Phone Number: 904-244-4986; Email: Faheem.Guirgis@jax.ufl.edu
    • Jacksonville, Florida, United States, 32218
      • Recruiting
      • UF Health Jacksonville North campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lipid; Infusion of drug (Smoflipid) will occur over a 16.5 hour period given once per day for the first two days of study enrollment.	Drug: Smoflipid; Administration of lipid injectable emulsion; Other Names: Total parenteral nutrition
No Intervention: Control; Control patients will receive no experimental drug (ie, usual care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Cholesterol	Delta total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL	48 hours
Maximum Tolerated Dose	Evaluate for dose limiting toxicities for the Phase I study	First 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Oxidation	HDL inflammatory index (ranges from 0-10)	48 hours
HDL function	Cholesterol efflux, this is a percentage from 0-100%	48 hours
Organ Dysfunction	Sequential Organ Failure Assessment (SOFA) Score, this is a numerical score ranging from 0 to 24	48 hours, 7 days
Mortality	Mortality	In-hospital, 28 day

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Faheem W Guirgis, MD, University of Florida

Publications and helpful links

General Publications

• Guirgis FW, Black LP, DeVos E, Henson M, Ferreira J, Miller T, Rosenthal M, Leeuwenburgh C, Kalynych C, Moldawer L, Jones L, Crandall M, Reddy ST, Gao H, Wu S, Moore F. Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial. J Am Coll Emerg Physicians Open. 2020 Nov 18;1(6):1332-1340. doi: 10.1002/emp2.12237. eCollection 2020 Dec.
• Guirgis FW, Black LP, Rosenthal MD, Henson M, Ferreira J, Leeuwenburgh C, Kalynych C, Moldawer LL, Miller T, Jones L, Crandall M, Reddy ST, Wu SS, Moore FA. LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock. BMJ Open. 2019 Sep 18;9(9):e029348. doi: 10.1136/bmjopen-2019-029348.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2018
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 12, 2018
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: lipids; cholesterol; total parenteral nutrition
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; SMOFlipid
• Other Study ID Numbers: IRB201800027 - A; OCR19642 (Other Identifier: UF OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No