Alirocumab in Patients with Sepsis

NCT05469347 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00004119
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Sepsis

Keywords

Sepsis; Septic shock; Respiratory failure; Vasopressors

Outcome Measures

Primary Outcomes (2)

• Bacterial endotoxin level

  Levels of bacterial endotoxin will be compared between study arms.

  Hour 120

• Lipoteichoic acid level

  Levels of lipoteichoic acid will be compared between study arms.

  Hour 120

Secondary Outcomes (9)

• Number of Vasopressor and Ventilation Free Days (VVFD)

  Up to Day 30

• Mortality

  Up to Day 30

• ICU Mortality

  Up to Day 30

• Days in ICU

  Up to Day 30

• Days in Hospital

  Up to Day 30

Study Arms (2)

Alirocumab

EXPERIMENTAL

Critically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive alirocumab.

Drug: Alirocumab

Placebo

PLACEBO COMPARATOR

Critically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive a placebo to match alirocumab.

Drug: Placebo

Interventions

Alirocumab DRUG

A 600 mg dose of alirocumab (which is equivalent to 8mg/kg for a 75kg patient) will be administered once via IV over an approximately 30 ± 10 minute infusion using an infusion pump.

Also known as: Praluent

Alirocumab

Placebo DRUG

A placebo to match a 600 mg dose of alirocumab will be administered once via IV over an approximately 30 ± 10 minute infusion using an infusion pump.

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Suspected or confirmed infection as evidenced by ordering of blood cultures and administration of at least one antimicrobial agent
• Acute respiratory or cardiovascular organ dysfunction attributed to sepsis as evidenced by at least one of the following requirements:
• Vasopressor Requirement - Continuous infusion of norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine or other vasopressor agents at any dose for greater than 1 hour and required to maintain a mean arterial pressure ≥ 65 mm Hg despite intravenous crystalloid infusion of at least 1000cc
• Respiratory Support Requirement - Acute hypoxemic respiratory failure defined as persistent hypoxemia requiring (1) intubation and mechanical ventilation, or (2) positive pressure ventilation via tight-fitting face mask or (3) high flow nasal cannula ≥ 45 liters per minute (LPM) flow and fraction of inspired oxygen (FiO2) ≥ 0.40
• Anticipated or confirmed intensive care unit (ICU) admission

You may not qualify if:

• Organ dysfunction present \> 24 hours at time randomization
• Development of sepsis while in the hospital ( i.e not present on admission to hospital)
• Chronic hypoxemia requiring supplemental non-invasive oxygen or home mechanical ventilation
• Chronic cardiovascular failure requiring home mechanical hemodynamic support or home chemical hemodynamic support
• Known allergy or known contraindication to alirocumab
• Chronic disease/illness that, in the opinion of the site investigator, have an expected lifespan of \< 30 days unrelated to current sepsis diagnosis (e.g, stage IV malignancy, neurodegenerative disease, etc.)
• Requirement of more than 6 liters (L) nasal cannula (NC) if not receiving invasive mechanical ventilation
• Pregnancy
• Prisoner or incarceration
• Current participation in another interventional pharmaceutical research study for sepsis
• Inability or unwillingness of subject or legal surrogate/representative to give written informed consent

Sponsors & Collaborators

• Jonathan Sevransky: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic; Respiratory Insufficiency

Interventions

alirocumab

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Jonathan Sevransky, MD, MHS

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: January 4, 2023
• Primary Completion: February 18, 2025
• Study Completion: February 23, 2025
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Individual participant data will be available for sharing one year after publication of the primary manuscript from this study.
• Access Criteria: Researchers interested in accessing data from this study should contact the study principal investigator.

Locations

US (2)