LIPIDS-P Trial Phase I/II Trial

NCT03405870 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB201800027 - AOCR19642
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 3

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).

Conditions

Sepsis, Severe; Septic Shock

Keywords

cholesterol; lipids; total parenteral nutrition

Outcome Measures

Primary Outcomes (2)

• Phase II - Primary Outcome - Change in Total Cholesterol (48 Hours - Enrollment)

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

  48 hours

• Phase I - Primary Outcome - Maximum Tolerated Dose/Participants Experiencing Dose Related Toxicity

  Using sequential dose escalation, participants received 2 doses of 1.0 to 1.6 g/kg of lipid emulsion (Smoflipid 20% lipid emulsion) within 48 hours of enrollment to test the maximum tolerated dose of study drug. The maximum tolerated dose was defined by patients exhibiting specific dose-related toxicities from administration of escalating doses of the study drug. Of 9 patients, adverse events were only considered dose-limiting toxicities if they met the predefined study protocol criteria. None of these were classified as dose limiting or serious.

  First 48 hours

Secondary Outcomes (1)

• Phase II - Secondary Outcome - Organ Dysfunction

  48 hours

Study Arms (8)

Phase II - 1.2 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase II - 1.4 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase II - 1.6 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase II - Control

NO INTERVENTION

No drug, patients will be followed as active controls

Phase I - 1.0 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase I - 1.2 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase I - 1.4 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Phase I - 1.6 g/kg Smoflipid

EXPERIMENTAL

Infusion of drug (Smoflipid) will occur over a 10-16.5 hour period given once per day for the first two days of study enrollment.

Drug: Smoflipid

Interventions

Smoflipid DRUG

Administration of lipid injectable emulsion

Also known as: Total parenteral nutrition

Phase I - 1.0 g/kg Smoflipid; Phase I - 1.2 g/kg Smoflipid; Phase I - 1.4 g/kg Smoflipid; Phase I - 1.6 g/kg Smoflipid; Phase II - 1.2 g/kg Smoflipid; Phase II - 1.4 g/kg Smoflipid; Phase II - 1.6 g/kg Smoflipid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead

Study Sites (3)

Department of Emergency Medicine, UF Health

Gainesville, Florida, 32610, United States

Location

UF Health Emergency Medicine

Gainesville, Florida, 32610, United States

Location

UF Health Jacksonville North campus

Jacksonville, Florida, 32218, United States

Location

Related Publications (4)

• Augustin B, Wu D, Black LP, Bertrand A, Sulaiman D, Hopson C, Jacob V, Shavit JA, Hofmaenner DA, Labilloy G, Smith L, Cagmat E, Graim K, Datta S, Reddy ST, Guirgis FW. Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality. Crit Care. 2024 Dec 24;28(1):431. doi: 10.1186/s13054-024-05216-3.

  PMID: 39716214 DERIVED

• Guirgis FW, Black LP, Henson M, Bertrand A, DeVos E, Ferreira J, Gao H, Wu SS, Leeuwenburgh C, Moldawer L, Moore F, Reddy ST. The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial. Crit Care Med. 2024 Aug 1;52(8):1183-1193. doi: 10.1097/CCM.0000000000006268. Epub 2024 Mar 15.

  PMID: 38488429 DERIVED

• 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.

  PMID: 33392541 DERIVED

• 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.

  PMID: 31537565 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic; Hyperphagia

Interventions

SMOFlipid; Parenteral Nutrition, Total

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Signs and Symptoms, Digestive; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Parenteral Nutrition; Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy

Limitations and Caveats

For the Phase I trial, the main limitation was the small sample of patients; however, this is not uncommon among phase I trials. The Phase II was also a small clinical trial of 47 patients, planned for 24 patients in each arm. Strict enrollment criteria limited enrollment in this study and the exclusion of patients with elevated bilirubin given the drug's hepatic metabolism and risk of complications limited the number of patients who could enroll.

Results Point of Contact

• Title: Dr. Faheem Guirgis, MD
• Organization: University of Florida College of Medicine

fguirgis@ufl.edu

352-733-1469

Study Officials

• Faheem W Guirgis, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Because this is a pilot study, and because the lipid emulsion appears white and was visible to the treatment team, the study was not blinded. Data abstractors were blinded to the treatment effect. As the treatment effects are objective measurements (lipid levels, SOFA score, etc.) the likelihood of bias is low.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study has a Phase I/II design. For the Phase I study, 10 patients were enrolled, and 9 completed the study. The Phase I study was designed to test the maximum tolerated dose of Smoflipid in escalating doses from 1.0 g/kg, 1.2 g/kg, 1.4 g/kg, and 1.6 g/kg. One patient withdrew from the study for social reasons. The Phase II trial was a randomized clinical trial to test the efficacy of 3 doses of study drug (1.2 g/kg, 1.4 g/kg, and 1.6 g/kg) for the primary outcome of cholesterol stabilization at 48 hours. 49 patients were enrolled and randomized. Two patients were withdrawn prior to drug. 47 patients completed the study protocol. Trial patients were randomized to receive either Smoflipid or control (no active treatment) using a Bayesian Optimal Interval Design. Thus, the Phase II arm included 24 patients in the control arm and 23 patients randomized to one of the three most efficacious doses of the study drug based on body weight, while the control group received no drug.

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: January 23, 2018
• Study Start: August 17, 2018
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: August 11, 2025
• Results First Posted: August 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)