Alirocumab in Patients with Sepsis

NCT ID: NCT05469347

Last Updated: 2025-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-04
• Study Completion Date: 2025-02-23

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.

Detailed 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.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Alirocumab

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Alirocumab

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Praluent

Eligibility Criteria

Inclusion Criteria

• 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

• 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

Exclusion Criteria

• Organ dysfunction present > 24 hours at time randomization

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Jonathan Sevransky

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Sevransky

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jonathan Sevransky, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

STUDY00004119

Identifier Type: -

Identifier Source: org_study_id