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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03405870
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : September 3, 2020
Fresenius Kabi
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Sepsis, Severe Septic Shock Drug: Smoflipid Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study has a Phase I/II design, with the first 16 patients enrolled in the study to evaluate for dose limiting toxicity (DLT). For the first 16 patients enrolled in the Phase I dose-escalation study, there will be no control group, with doses starting at 1.0g/kg and increasing incrementally based on weight by 0.2g/kg to a maximum dose of 1.8g/kg. Dose escalation or de-escalation will occur based on whether DLTs are observed at a specific dose, with the threshold for toxicity set at 10%. After evaluating for DLT, the two highest and safest doses will be used to randomize the remaining 48 patients into the Phase II study to either Smoflipid or control (no active treatment) using a Bayesian Optimal Interval Design. Thus, the Phase II arm will include 24 patients randomized to one of the two most efficacious doses of the study drug based on body weight, while the control group will receive no drug.
Masking: Single (Outcomes Assessor)
Masking Description: Because this is a pilot study, and because the lipid emulsion appears white and will be visible to the treatment team, the study will not be blinded. Data abstractors will, however, be blinded to the treatment effect. As the treatment effects are objective measurements (lipid levels, SOFA score, etc.) the likelihood of bias is low.
Primary Purpose: Treatment
Official Title: The LIPid Intensive Drug Therapy for Sepsis ¬Pilot (LIPIDS-P) Phase I/II Trial
Actual Study Start Date : August 17, 2018
Estimated Primary Completion Date : February 11, 2021
Estimated Study Completion Date : February 11, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: SMOFlipid

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 Name: Total parenteral nutrition

No Intervention: Control
Control patients will receive no experimental drug (ie, usual care)

Primary Outcome Measures :
  1. Total Cholesterol [ Time Frame: 48 hours ]
    Delta total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL

  2. Maximum Tolerated Dose [ Time Frame: First 7 days ]
    Evaluate for dose limiting toxicities for the Phase I study

Secondary Outcome Measures :
  1. Lipid Oxidation [ Time Frame: 48 hours ]
    HDL inflammatory index (ranges from 0-10)

  2. HDL function [ Time Frame: 48 hours ]
    Cholesterol efflux, this is a percentage from 0-100%

  3. Organ Dysfunction [ Time Frame: 48 hours, 7 days ]
    Sequential Organ Failure Assessment (SOFA) Score, this is a numerical score ranging from 0 to 24

  4. Mortality [ Time Frame: In-hospital, 28 day ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03405870

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Contact: Faheem W Guirgis, MD 904-244-4986
Contact: Colleen Kalynych, MSH, EdD 904-244-8605

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United States, Florida
Department of Emergency Medicine, UF Health Jax ICU/MICU Recruiting
Jacksonville, Florida, United States, 32209
Contact: Faheem Guirgis, MD    904-244-4986   
Contact: Colleen Kalynych, MSH, EdD    904-244-8605   
UF Health Jacksonville Recruiting
Jacksonville, Florida, United States, 32209
Contact: Faheem Guirgis, MD    904-244-4986   
Contact: Colleen Kalynych, MSH, EdD    904-244-8605   
UF Health Jacksonville North campus Recruiting
Jacksonville, Florida, United States, 32218
Sponsors and Collaborators
University of Florida
Fresenius Kabi
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Principal Investigator: Faheem W Guirgis, MD University of Florida
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Florida Identifier: NCT03405870    
Other Study ID Numbers: IRB201800027 - A
OCR19642 ( Other Identifier: UF OnCore )
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by University of Florida:
total parenteral nutrition
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Pathologic Processes