SepsisPhase 1PALMSNCT05469347
Alirocumab in Patients with Sepsis
A Phase 1 study testing Alirocumab in people with Sepsis, run by Jonathan Sevransky at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Sepsis
- What is being tested?
- Alirocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Jan 2023to 23 Feb 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Organ dysfunction present > 24 hours at time randomization
- Limitations of care (defined as refusal of cardiovascular and respiratory support described under inclusion criteria) including "do not intubate" (DNI) status
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Grady Memorial Hospital
Atlanta, Georgia, 30303
Emory University Hospital
Atlanta, Georgia, 30322
About this study
Official title: PCSK9 and Lipid Metabolism in Sepsis (PALMS) : a Two-center, Phase 1b Randomized, Placebo-controlled, Double-blind, Clinical Trial of Alirocumab in Patients with Sepsis
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.
Read the 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
- Being tested
- Alirocumab, Placebo
- Keywords
- Sepsis, Septic shock, Respiratory failure, Vasopressors
- Medical subject headings
- Sepsis, Shock, Septic, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Also called Praluent
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Alirocumab | Experimental | Critically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive alirocumab. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bacterial endotoxin level
Levels of bacterial endotoxin will be compared between study arms.
Measured: Hour 120
Lipoteichoic acid level
Levels of lipoteichoic acid will be compared between study arms.
Measured: Hour 120
Secondary outcomes (9)
Number of Vasopressor and Ventilation Free Days (VVFD)
The number of consecutive days free of vasopressors and mechanical ventilation (VVFD) will be compared between study arms. Ventilator and vasopressor free days will only accrue from the last date the participant was free of both ventilator and vasopressor support. Participants who die are scored zero VVFD, and participants who return to ventilator support or vasopressor support will have the VVFD count reset to zero days.
Measured: Up to Day 30
Mortality
The number of participants who die will be compared between study arms.
Measured: Up to Day 30
ICU Mortality
The number of participants who die while in the ICU will be compared between study arms.
Measured: Up to Day 30
Days in ICU
Length of stay in the ICU (measured in days) will be compared between study arms.
Measured: Up to Day 30
Days in Hospital
Length of stay in the hospital (measured in days) will be compared between study arms.
Measured: Up to Day 30
Tumor necrosis factor - alpha (TNF-alpha) Level
The level of the proinflammatory cytokine TNF will be compared between study arms. Higher levels of TNF are associated with poorer outcomes in patients with sepsis.
Measured: Hour 120
Interleukin-1 beta (IL-1 beta) Level
The level of the proinflammatory cytokine IL-1 will be compared between study arms. Higher levels of IL-1 are associated with poorer outcomes in patients with sepsis.
Measured: Hour 120
Interleukin-6 (IL-6) Level
The level of the proinflammatory cytokine IL-6 will be compared between study arms. Higher levels of IL-6 are associated with poorer outcomes in patients with sepsis.
Measured: Hour 120
Interleukin-10 (IL-10) Level
The level of the proinflammatory cytokine IL-10 will be compared between study arms. Higher levels of IL-10 are associated with poorer outcomes in patients with sepsis.
Measured: Hour 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study start4 Jan 2023
- Primary completion18 Feb 2025
- Study completion23 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonathan Sevransky
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor-investigator, Jonathan Sevransky, Emory University
- Investigators
- Jonathan Sevransky, MD, MHS, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05469347
- Sponsor's protocol ID
- STUDY00004119
- Acronym
- PALMS
- Status last verified
- Mar 2025
- First submitted
- 19 Jul 2022
- Last updated
- 24 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data is shared with the funding source (Regeneron) and data will be made available for sharing with other researchers upon request.
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PCSK9 and Lipid Metabolism in Sepsis (PALMS) : a Two-center, Phase 1b Randomized, Placebo-controlled, Double-blind, Clinical Trial of Alirocumab in Patients with Sepsis
- ClinicalTrials.gov ID
- NCT05469347
- Acronym / sponsor ID
- PALMS / STUDY00004119
- Conditions
- Sepsis
- Keywords
- Sepsis, Septic shock, Respiratory failure, Vasopressors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Jonathan SevranskyUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 4 Jan 2023 (actual)
- Primary completion
- 18 Feb 2025 (actual)
- Study completion
- 23 Feb 2025 (actual)
- First posted
- 21 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alirocumab | Experimental | Drug: AlirocumabCritically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive alirocumab. |
| Placebo | Placebo comparator | Drug: PlaceboCritically ill participants with sepsis leading to cardiovascular and/or respiratory failure who are randomized to receive a placebo to match alirocumab. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- Anticipated or confirmed intensive care unit (ICU) admission
Key exclusion criteria (12 listed)
- Organ dysfunction present > 24 hours at time randomization
- Limitations of care (defined as refusal of cardiovascular and respiratory support described under inclusion criteria) including "do not intubate" (DNI) status
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlirocumabAlso: PraluentA 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. | Drug | Alirocumab |
| PlaceboA 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. | Drug | Placebo |
Primary outcome
Bacterial endotoxin level
Time frame: Hour 120
Levels of bacterial endotoxin will be compared between study arms.
Lipoteichoic acid level
Time frame: Hour 120
Levels of lipoteichoic acid will be compared between study arms.
9 secondary outcomes
Number of Vasopressor and Ventilation Free Days (VVFD)
Time frame: Up to Day 30
Mortality
Time frame: Up to Day 30
ICU Mortality
Time frame: Up to Day 30
Days in ICU
Time frame: Up to Day 30
Days in Hospital
Time frame: Up to Day 30
Tumor necrosis factor - alpha (TNF-alpha) Level
Time frame: Hour 120
Interleukin-1 beta (IL-1 beta) Level
Time frame: Hour 120
Interleukin-6 (IL-6) Level
Time frame: Hour 120
Interleukin-10 (IL-10) Level
Time frame: Hour 120
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data is shared with the funding source (Regeneron) and data will be made available for sharing with other researchers upon request.
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Sevransky, MD, MHS principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alirocumab in people with Sepsis, run by Jonathan Sevransky at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bacterial endotoxin level (time frame: Hour 120). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025; AzTrials last refreshed its copy on 6 Nov 2026.