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LIPIDS-P Trial Phase I/II

Sponsor
University of Florida (Other)
Overall Status
Recruiting
CT.gov ID
NCT03405870
Collaborator
(none)
68
Enrollment
3
Locations
2
Arms
51.5
Anticipated Duration (Months)
22.7
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
68 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The study has a Phase I/II design. For the Phase I, which has been completed, 10 patients were enrolled in the study to evaluate for dose limiting toxicity (DLT). For patients enrolled in the Phase I dose-escalation study, there was 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 1.6g/kg. Dose escalation or de-escalation occurred based on whether DLTs were 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 per arm 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.The study has a Phase I/II design. For the Phase I, which has been completed, 10 patients were enrolled in the study to evaluate for dose limiting toxicity (DLT). For patients enrolled in the Phase I dose-escalation study, there was 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 1.6g/kg. Dose escalation or de-escalation occurred based on whether DLTs were 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 per arm 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 :
Aug 17, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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)

    Outcome Measures

    Primary Outcome Measures

    1. Total Cholesterol [48 hours]

      Delta total cholesterol (48 hour - enrollment value) of 0 to +5 mg/dL

    2. Maximum Tolerated Dose [First 7 days]

      Evaluate for dose limiting toxicities for the Phase I study

    Secondary Outcome Measures

    1. Lipid Oxidation [48 hours]

      HDL inflammatory index (ranges from 0-10)

    2. HDL function [48 hours]

      Cholesterol efflux, this is a percentage from 0-100%

    3. Organ Dysfunction [48 hours, 7 days]

      Sequential Organ Failure Assessment (SOFA) Score, this is a numerical score ranging from 0 to 24

    4. Mortality [In-hospital, 28 day]

      Mortality

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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,

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

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

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

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

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

    6. severe primary blood coagulation disorder,

    7. acute pancreatitis accompanied by hyperlipidemia,

    8. acute thromboembolic disease,

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

    10. 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),

    11. pregnancy or lactation

    12. 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.

    13. Child Pugh Class B/C liver disease patients or liver transplant recipient

    14. Patients on, or anticipated to be placed on, ECMO within 48 hours of enrollment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Department of Emergency Medicine, UF Health Jax ICU/MICU Jacksonville Florida United States 32209
    2 UF Health Jacksonville Jacksonville Florida United States 32209
    3 UF Health Jacksonville North campus Jacksonville Florida United States 32218

    Sponsors and Collaborators

    • University of Florida

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT03405870
    Other Study ID Numbers:
    • IRB201800027 - A
    • OCR19642
    First Posted:
    Jan 23, 2018
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    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
    cholesterol
    lipids
    total parenteral nutrition
    Additional relevant MeSH terms:
    Sepsis
    SMOFlipid

    Study Results

    No Results Posted as of Jan 12, 2022