Alirocumab in Patients with Sepsis

Last updated: March 20, 2025
Sponsor: Jonathan Sevransky
Overall Status: Completed

Phase

1

Condition

Soft Tissue Infections

Treatment

Placebo

Alirocumab

Clinical Study ID

NCT05469347
STUDY00004119
  • Ages 18-90
  • All Genders

Study Summary

The purpose of this study is to determine whether the drug alirocumab, which may lower cholesterol, can reduce the amount of inflammation caused by an infection that has caused either low blood pressure or difficulty breathing. Participants will be randomized to receive a single IV infusion of alirocumab or a placebo.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Suspected or confirmed infection as evidenced by ordering of blood cultures andadministration of at least one antimicrobial agent

  • Acute respiratory or cardiovascular organ dysfunction attributed to sepsis asevidenced by at least one of the following requirements:

  • Vasopressor Requirement - Continuous infusion of norepinephrine, epinephrine,vasopressin, dopamine, phenylephrine or other vasopressor agents at any dosefor greater than 1 hour and required to maintain a mean arterial pressure ≥ 65mm Hg despite intravenous crystalloid infusion of at least 1000cc

  • Respiratory Support Requirement - Acute hypoxemic respiratory failure definedas persistent hypoxemia requiring (1) intubation and mechanical ventilation, or (2) positive pressure ventilation via tight-fitting face mask or (3) high flownasal cannula ≥ 45 liters per minute (LPM) flow and fraction of inspired oxygen (FiO2) ≥ 0.40

  • Anticipated or confirmed intensive care unit (ICU) admission

Exclusion

Exclusion Criteria:

  • Organ dysfunction present > 24 hours at time randomization

  • Limitations of care (defined as refusal of cardiovascular and respiratory supportdescribed under inclusion criteria) including "do not intubate" (DNI) status

  • Development of sepsis while in the hospital ( i.e not present on admission tohospital)

  • Chronic hypoxemia requiring supplemental non-invasive oxygen or home mechanicalventilation

  • Chronic cardiovascular failure requiring home mechanical hemodynamic support or homechemical hemodynamic support

  • Known allergy or known contraindication to alirocumab

  • Chronic disease/illness that, in the opinion of the site investigator, have anexpected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g, stage IVmalignancy, neurodegenerative disease, etc.)

  • Requirement of more than 6 liters (L) nasal cannula (NC) if not receiving invasivemechanical ventilation

  • Pregnancy

  • Prisoner or incarceration

  • Current participation in another interventional pharmaceutical research study forsepsis

  • Inability or unwillingness of subject or legal surrogate/representative to givewritten informed consent

Study Design

Total Participants: 50
Treatment Group(s): 2
Primary Treatment: Placebo
Phase: 1
Study Start date:
January 04, 2023
Estimated Completion Date:
February 23, 2025

Study Description

Sepsis is an inflammatory syndrome with life threatening organ dysfunction resulting from a dysregulated host response to infection. The global burden is estimated to exceed 15 million cases annually. In the United States, the incidence is increasing and currently there are more 1,750,000 cases each year, with more than half requiring intensive care unit (ICU) admission. Further, sepsis cases account for 30%- 50% of all hospital deaths, making it the third leading cause of death in the United States, and is the most expensive reason for hospitalization with annual expenditures exceeding $20 billion. Notably, even among those that do survive, many endure significant reductions in physical, emotional and cognitive quality of life. New therapeutic approaches to reduce the high morbidity and mortality of sepsis are needed.

Current management strategies focus on early aggressive fluid resuscitation, blood pressure support with vasopressors, early appropriate antibiotics, and the identification and control of infected sites. Though outcomes have improved with the bundled deployment of these strategies, mortality remains high at 20 - 30%. Despite over a hundred phase 2 and phase 3 clinical trials of pharmacological agents with the potential to improve sepsis outcomes, only antibiotics have demonstrated reproducible benefits.

Despite decades of research, no specific treatment of the dysregulated host response has proven effective. There is strong biologic plausibility to modulate the PCSK9 pathway in sepsis patients. Alirocumab is a PCSK9 inhibitor that has been shown to reduce LDL cholesterol in normal volunteers and in patients with familial hypercholesterolemia.

Patients admitted to a study site hospital with sepsis or septic shock associated with cardiovascular or respiratory failure will be considered for enrollment. Those meeting eligibility criteria and providing consent for study participation will be randomized to receive alirocumab or a placebo, administered once via IV over an approximately 30 ± 10 minute infusion. Participants will be followed for 180 days.

Connect with a study center

  • Emory University Hospital

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Grady Memorial Hospital

    Atlanta, Georgia 30303
    United States

    Site Not Available

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