LIPIDS-P Trial Phase I/II Trial

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-17

Study Completion Date

2023-04-26

Brief Summary

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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).

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Detailed Description

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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.

Conditions

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Sepsis, Severe Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

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.

Study Groups

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Phase II - 1.2 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase II - 1.4 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase II - 1.6 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase II - Control

No drug, patients will be followed as active controls

Group Type NO_INTERVENTION

No interventions assigned to this group

Phase I - 1.0 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase I - 1.2 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase I - 1.4 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Phase I - 1.6 g/kg Smoflipid

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.

Group Type EXPERIMENTAL

Smoflipid

Intervention Type DRUG

Administration of lipid injectable emulsion

Interventions

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Smoflipid

Administration of lipid injectable emulsion

Intervention Type DRUG

Other Intervention Names

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Total parenteral nutrition

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No