LIPIDS-P Trial Phase I/II Trial

University of Florida

Status and phase: Completed; Phase 2; Phase 1

Conditions: Sepsis, Severe; Septic Shock

Treatments: Drug: Smoflipid

Study type: Interventional

Funder types: Other

Identifiers

NCT03405870

OCR19642 (Other Identifier)

IRB201800027 - A

Details and patient eligibility

About

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).

Full 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.

Enrollment: 59 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

59 participants in 8 patient groups

Phase II - 1.2 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase II - 1.4 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase II - 1.6 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase II - Control

No Intervention group

Description:

No drug, patients will be followed as active controls

Phase I - 1.0 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase I - 1.2 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase I - 1.4 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid

Phase I - 1.6 g/kg Smoflipid

Experimental group

Description:

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.

Treatment:

Drug: Smoflipid