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

Primary Purpose

Sepsis, Severe, Septic Shock

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Smoflipid

About this trial

This is an interventional treatment trial for Sepsis, Severe focused on measuring cholesterol, lipids, total parenteral nutrition

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

age > 18,
primary diagnosis of sepsis and within 24 hours of sepsis recognition and treated with institutional sepsis algorithm,
SOFA score ≥ 4,
screening total cholesterol ≤ 100 mg/dL or HDL-C + LDL-C ≤ 70 mg/dL

Exclusion Criteria:

total bilirubin > 2 mg/dL,
serum albumin < 1.5 mg/dL,
hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients,
severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 400 mg/dL,
alternative/confounding diagnosis causing shock or critical illness (e.g., myocardial infarction or pulmonary embolus, massive hemorrhage, trauma),
significant traumatic brain injury (evidence of neurologic injury on CT scan and a GCS <8),
refractory shock (likely death within 12 hours),
established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable,
anticipated requirement for surgery that would interfere with drug infusion,
severe primary blood coagulation disorder,
acute pancreatitis accompanied by hyperlipidemia,
acute thromboembolic disease,
uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel),
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),
pregnancy or lactation
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.
Child Pugh Class B/C liver disease patients or liver transplant recipient
Patients on, or anticipated to be placed on, ECMO within 48 hours of enrollment

Sites / Locations

Department of Emergency Medicine, UF Health Jax ICU/MICURecruiting
UF Health JacksonvilleRecruiting
UF Health Jacksonville North campusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Lipid

Control

Arm Description

Infusion of drug (Smoflipid) will occur over a 16.5 hour period given once per day for the first two days of study enrollment.

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

Outcomes

Primary Outcome Measures

Total Cholesterol

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

Maximum Tolerated Dose

Evaluate for dose limiting toxicities for the Phase I study

Secondary Outcome Measures

Lipid Oxidation

HDL inflammatory index (ranges from 0-10)

HDL function

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

Organ Dysfunction

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

Mortality

Full Information

NCT ID

NCT03405870

First Posted

January 12, 2018

Last Updated

January 10, 2022

Sponsor

University of Florida

1. Study Identification

Unique Protocol Identification Number

NCT03405870

Brief Title

LIPIDS-P Trial Phase I/II

Acronym

LIPIDS-P

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 17, 2018 (Actual)

Primary Completion Date

December 1, 2022 (Anticipated)

Study Completion Date

December 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis, Severe, Septic Shock

Keywords

cholesterol, lipids, total parenteral nutrition

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

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.

Masking

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.

Allocation

Randomized

Enrollment

68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Lipid

Arm Type

Experimental

Arm Description

Infusion of drug (Smoflipid) will occur over a 16.5 hour period given once per day for the first two days of study enrollment.

Arm Title

Control

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Smoflipid

Other Intervention Name(s)

Total parenteral nutrition

Intervention Description

Administration of lipid injectable emulsion

Primary Outcome Measure Information:

Title

Total Cholesterol

Description

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

Time Frame

48 hours

Title

Maximum Tolerated Dose

Description

Evaluate for dose limiting toxicities for the Phase I study

Time Frame

First 7 days

Secondary Outcome Measure Information:

Title

Lipid Oxidation

Description

HDL inflammatory index (ranges from 0-10)

Time Frame

48 hours

Title

HDL function

Description

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

Time Frame

48 hours

Title

Organ Dysfunction

Description

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

Time Frame

48 hours, 7 days

Title

Mortality

Description

Mortality

Time Frame

In-hospital, 28 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: age > 18, primary diagnosis of sepsis and within 24 hours of sepsis recognition and treated with institutional sepsis algorithm, SOFA score ≥ 4, screening total cholesterol ≤ 100 mg/dL or HDL-C + LDL-C ≤ 70 mg/dL Exclusion Criteria: total bilirubin > 2 mg/dL, serum albumin < 1.5 mg/dL, hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients, severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 400 mg/dL, alternative/confounding diagnosis causing shock or critical illness (e.g., myocardial infarction or pulmonary embolus, massive hemorrhage, trauma), significant traumatic brain injury (evidence of neurologic injury on CT scan and a GCS <8), refractory shock (likely death within 12 hours), established Do Not Resuscitate status or advanced directives restricting aggressive care or treating physician deems aggressive care unsuitable, anticipated requirement for surgery that would interfere with drug infusion, severe primary blood coagulation disorder, acute pancreatitis accompanied by hyperlipidemia, acute thromboembolic disease, uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel), 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), pregnancy or lactation 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. Child Pugh Class B/C liver disease patients or liver transplant recipient Patients on, or anticipated to be placed on, ECMO within 48 hours of enrollment

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Faheem W Guirgis, MD

Phone

904-244-4986

faheem.guirgis@jax.ufl.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Morgan Henson, MPH

Phone

904-244-4234

Morgan.Henson@jax.ufl.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Faheem W Guirgis, MD

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Emergency Medicine, UF Health Jax ICU/MICU

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Faheem Guirgis, MD

Phone

904-244-4986

Faheem.Guirgis@jax.ufl.edu

First Name & Middle Initial & Last Name & Degree

Morgan Henson, MPH

Phone

904-244-4234

Morgan.Henson@jax.ufl.edu

Facility Name

UF Health Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Faheem Guirgis, MD

Phone

904-244-4986

Faheem.Guirgis@jax.ufl.edu

First Name & Middle Initial & Last Name & Degree

Morgan Henson, MPH

Phone

904-244-4234

Morgan.Henson@jax.ufl.edu

Facility Name

UF Health Jacksonville North campus

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32218

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

33392541

Citation

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.

Results Reference

derived

PubMed Identifier

31537565

Citation

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.

Results Reference

derived

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LIPIDS-P Trial Phase I/II

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