SepsisPhase 2PLEASeNCT03869073
Evolocumab for PCSK9 Lowering in Early Acute Sepsis (The PLEASe Study)
A Phase 2 study testing Evolocumab in people with Sepsis, run by University of British Columbia at 3 sites in Canada.
Trial summary
This study evaluates using evolocumab, a currently approved and marketed biologic drug, in a novel way. Patients who present to the emergency room or intensive care unit (ICU) with severe infection are eligible. Either the patient or their designated decision maker will be approached for consent. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 3 sitesCanada
- Study dates
- 11 Feb 2019to 11 Feb 2021
- Phase
- Phase 2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- At least 19 years of age
- Known or suspected infection
- AND one or more of the following organ dysfunctions judged due to sepsis:
- Cardiovascular- refractory hypotension (a systolic blood pressure (SBP) < 90 mm Hg or mean arterial pressure (MAP) < 60 mm Hg despite an IV fluid challenge of at least 30 ml/kg fluids), or use of vasopressor(s) to maintain SAP > 90 mm Hg or MAP > 60 mm Hg, or;
- Respiratory: PaO2/FiO2 < 300 or PaO2/FiO2 < 200 if lung is the only organ dysfunction or SaO2:FiO2 150
Who cannot join
- Known pregnancy
- Underlying severe congestive heart failure (New York Heart Association (NYHA) IV), severe COPD (need for chronic oxygen or mechanical ventilation), severe liver disease (Child-Pugh Class C), cancer requiring chemotherapy, or transplantation (bone marrow, heart, lung, liver, pancreas, or small bowel) in the past 6 months or likely within the next 6 months
- Previous episode of sepsis during that hospital admission
- Absolute Neutrophil Count < 500/mm³
- CD4 count < 50/mm³
- Treating physician deems aggressive care unsuitable (i.e. no commitment to active care)
Show all 10Show fewer
- Participation in another interventional drug study within previous 1 month
- Allergic to the study drug or any of its components
- Lactation
- Have signed a Do No Resuscitate (DNR) Form
Trial locations and contacts
3 sites in 1 country.
Lynda Lazosky contact
Canada3 sites, 3 recruiting
- Not yet recruiting
Surrey Memorial Hospital
Surrey, British Columbia, V3V 1Z2
Gregory Haljan, MD
- Recruiting
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
John Boyd, MD
- Not yet recruiting
Vancouver General Hospital
Vancouver, British Columbia, V6Z 1Y6
Donald Griesdale, MD
About this study
Official title: Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Efficacy and Safety of Evolocumab for PCSK9 Lowering in Early Acute Sepsis
This study evaluates using evolocumab, a currently approved and marketed biologic drug, in a novel way. Patients who present to the emergency room or intensive care unit (ICU) with severe infection are eligible. Either the patient or their designated decision maker will be approached for consent. If they choose to participate they will be given either a single dose of evolocumab, a higher single dose of evolocumab,or a single dose of placebo. Participants will be followed during their stay in the ICU and will receive follow up phone calls at Day 28 and 90.
Read the detailed description
Evolocumab is currently approved and marketed in USA and Canada for lowering cholesterol levels. Evolocumab is an anti-PSCK9 monoclonal antibody, and functions by binding PSCK9 (an inhibitor of LDL removal) and blocking its function. Evidence suggests that since evolocumab increases the removal rate of low-density lipoproteins from the body, it might also help increase the removal of bacterial components that are attached to circulating lipids during sepsis. Quickly removing these bacterial components could prevent a strong and rapid immune response that often leads to organ failure and death in sepsis patients.
- Conditions
- Sepsis
- Being tested
- Evolocumab, Placebo
- Keywords
- Bacterial, Infection, Blood, Systemic, ICU
- Medical subject headings
- Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha
Three pre-filled shrouded syringes for subcutaneous injection in abdomen.
PlaceboDrug
Also called Saline
Preservative free 0.9% sodium chloride. Three pre-filled shrouded syringes for subcutaneous injection in abdomen.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | This treatment arm will receive the highest dose of evolocumab currently marketed and approved: 420mg. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. Receives: Drug: Evolocumab |
| High Dose | Experimental | This treatment arm will receive double the highest dose of evolocumab currently marketed and approved: 840mg. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. Receives: Drug: Evolocumab |
| Placebo | Placebo comparator | This treatment arm will receive saline solution. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma LTA and LPS curves
Determine whether evolocumab decreases plasma levels of bacterial LPS and LTA, at 6, 24, 48 and 72 hours, and day 7 by comparing the area under the operating curve between arms.
Measured: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Secondary outcomes (24)
Levels of LDL-C
Measure levels (concentration; e.g. ug/mL) of low-density lipoprotein-cholesterol (LDL-C) at 24, 48, and 72 hours, and day 7, and compare area under the plasma cytokine curve between arms.
Measured: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Levels of cytokines IL-6, TNF-alpha and IL-8
Measure levels (concentration; e.g. ug/mL) of cytokines (IL-6, TNF-alpha and IL-8) at 24, 48, and 72 hours, and day 7, and compare area under the plasma cytokine curve between arms.
Measured: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Concentration of circulating evolocumab and circulating free PCSK9 in septic patients
Assess the concentration (e.g. umol/L) of circulating evolocumab and free (unbound by antibody) PCSK9 in evolocumab-treated patients with sepsis and compare to placebo controls.
Measured: 7 days or less (may be discharged from critical care before day 7)
Cmax of circulating evolocumab and circulating free PCSK9 in septic patients
Assess the Cmax of circulating evolocumab and free (unbound by antibody) PCSK9 in evolocumab-treated patients with sepsis and compare to placebo controls.
Measured: 7 days or less (may be discharged from critical care before day 7)
Days alive
Determine if changes in days alive over 28 days are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in 28-day mortality
Determine whether differences in mortality rates at 28 days exist between treatment arms.
Measured: 28 days
Level of organ dysfunction
Determine if changes in days free of organ dysfunction (cardiovascular, respiratory, renal, hematologic, and hepatic) over 28 days are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Level of organ support
Determine if changes in days free of organ support (vasopressor, ventilation and renal replacement therapy (RRT)) over 28 days are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: lactate
Determine if changes in plasma lactate levels (mmol/L) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: norepinephrine dose
Determine if changes in norepinephrine levels (mcg/min) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: mean arterial pressure
Determine if changes in mean arterial pressure levels (mm Hg) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: heart rate
Determine if changes in heart rate (beats per minute) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: respiratory rate
Determine if changes in respiratory rate (breaths per minute) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: temperature
Determine if changes in temperature (degrees Celsius) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: fluid balance
Determine if changes in fluid balance (Liters) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: urine output
Determine if changes in urine output (Liters) are associated with treatment arm.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: Number of treatment-related adverse events as ranked by severity
Monitor and count by category, and evaluate severity and seriousness of any adverse events related to the intervention that occurs in this critical and previously untested population.
Measured: Day 1 to Day 90
Safety outcomes: changes in blood cell counts
Document changes in blood cell counts (cells/ml) including white blood cells, red blood cells, and platelets, and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in coagulation
Document changes in coagulation of blood by measuring Prothrombin Time (PT) and Partial Thromboplastin Time (PTT). Both measurements determine time to clotting (in seconds) of different clotting factors and are then used to calculate International Normalized Ratio (INR) which helps monitor effects of blood thinning medication, and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in blood analytes
Document changes in concentration (e.g. umol/mL) of blood analytes, including hemoglobin, glucose, glycated hemoglobin, potassium, sodium, chloride, bicarbonate, creatinine, calcium, triponine, magnesium, aminotransferase, and alanine aminotransferase, and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in urine density
Document changes in urine specific gravity (density relative to water) and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in urine pH
Document changes in urine pH and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in concentration of ketones in urine
Document changes in concentration of ketones (e.g. umol/L) in the urine and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: document other urine abnormalities if required
Document presence of blood, nitrites, bacteria, or urinary casts in the urine (yes or no) and determine whether clinically significant changes are associated with treatment.
Measured: 28 days or less (may be discharged from critical care before day 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2019
- Study start11 Feb 2019
- Primary completion11 Feb 2021 (estimated)
- Study completion11 Feb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Upon enrolling in the study participants will be randomized into one of three possible treatment arms: 420mg single dose at baseline, 840mg single dose at baseline, or placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, john boyd, University of British Columbia
- Investigators
- John Boyd, MD, Principal investigator, University of British Columbia, Providence Health Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03869073
- Sponsor's protocol ID
- H18-00917
- Acronym
- PLEASe
- Status last verified
- Mar 2020
- First submitted
- 5 Mar 2019
- Last updated
- 3 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cirstea M, Walley KR, Russell JA, Brunham LR, Genga KR, Boyd JH. Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis. J Crit Care. 2017 Apr;38:289-294. doi: 10.1016/j.jcrc.2016.11.041. Epub 2016 Dec 7.
PubMed 28013095Roveran Genga K, Lo C, Cirstea M, Zhou G, Walley KR, Russell JA, Levin A, Boyd JH. Two-year follow-up of patients with septic shock presenting with low HDL: the effect upon acute kidney injury, death and estimated glomerular filtration rate. J Intern Med. 2017 May;281(5):518-529. doi: 10.1111/joim.12601. Epub 2017 Mar 19.
PubMed 28317295Levels JH, Abraham PR, van den Ende A, van Deventer SJ. Distribution and kinetics of lipoprotein-bound endotoxin. Infect Immun. 2001 May;69(5):2821-8. doi: 10.1128/IAI.69.5.2821-2828.2001.
PubMed 11292694Levels JH, Abraham PR, van Barreveld EP, Meijers JC, van Deventer SJ. Distribution and kinetics of lipoprotein-bound lipoteichoic acid. Infect Immun. 2003 Jun;71(6):3280-4. doi: 10.1128/IAI.71.6.3280-3284.2003.
PubMed 12761109Levels JH, Marquart JA, Abraham PR, van den Ende AE, Molhuizen HO, van Deventer SJ, Meijers JC. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun. 2005 Apr;73(4):2321-6. doi: 10.1128/IAI.73.4.2321-2326.2005.
PubMed 15784577Topchiy E, Cirstea M, Kong HJ, Boyd JH, Wang Y, Russell JA, Walley KR. Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor. PLoS One. 2016 May 12;11(5):e0155030. doi: 10.1371/journal.pone.0155030. eCollection 2016.
PubMed 27171436Walley KR, Thain KR, Russell JA, Reilly MP, Meyer NJ, Ferguson JF, Christie JD, Nakada TA, Fjell CD, Thair SA, Cirstea MS, Boyd JH. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014 Oct 15;6(258):258ra143. doi: 10.1126/scitranslmed.3008782.
PubMed 25320235Boyd JH, Fjell CD, Russell JA, Sirounis D, Cirstea MS, Walley KR. Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis. J Innate Immun. 2016;8(2):211-20. doi: 10.1159/000442976. Epub 2016 Jan 13.
PubMed 26756586
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Efficacy and Safety of Evolocumab for PCSK9 Lowering in Early Acute Sepsis
- ClinicalTrials.gov ID
- NCT03869073
- Acronym / sponsor ID
- PLEASe / H18-00917
- Conditions
- Sepsis
- Keywords
- Bacterial, Infection, Blood, Systemic, ICU
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 11 Feb 2021 (estimated)
- Study completion
- 11 Feb 2021 (estimated)
- First posted
- 11 Mar 2019 (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.
This study evaluates using evolocumab, a currently approved and marketed biologic drug, in a novel way. Patients who present to the emergency room or intensive care unit (ICU) with severe infection are eligible. Either the patient or their designated decision maker will be approached for consent. If they choose to participate they will be given either a single dose of evolocumab, a higher single dose of evolocumab,or a single dose of placebo. Participants will be followed during their stay in the ICU and will receive follow up phone calls at Day 28 and 90.
Detailed description
Evolocumab is currently approved and marketed in USA and Canada for lowering cholesterol levels. Evolocumab is an anti-PSCK9 monoclonal antibody, and functions by binding PSCK9 (an inhibitor of LDL removal) and blocking its function. Evidence suggests that since evolocumab increases the removal rate of low-density lipoproteins from the body, it might also help increase the removal of bacterial components that are attached to circulating lipids during sepsis. Quickly removing these bacterial components could prevent a strong and rapid immune response that often leads to organ failure and death in sepsis patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- Upon enrolling in the study participants will be randomized into one of three possible treatment arms: 420mg single dose at baseline, 840mg single dose at baseline, or placebo
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Drug: EvolocumabThis treatment arm will receive the highest dose of evolocumab currently marketed and approved: 420mg. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. |
| High Dose | Experimental | Drug: EvolocumabThis treatment arm will receive double the highest dose of evolocumab currently marketed and approved: 840mg. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. |
| Placebo | Placebo comparator | Drug: PlaceboThis treatment arm will receive saline solution. The dose will be given at a single time point within 4 hours of randomization. The dose will be administered through three subcutaneous injections, each in a different quadrant of the abdomen. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Signed informed consent
- At least 19 years of age
- Known or suspected infection
- AND one or more of the following organ dysfunctions judged due to sepsis:
Key exclusion criteria (10 listed)
- Known pregnancy
- Underlying severe congestive heart failure (New York Heart Association (NYHA) IV), severe COPD (need for chronic oxygen or mechanical ventilation), severe liver disease (Child-Pugh Class C), cancer requiring chemotherapy, or transplantation (bone marrow, heart, lung, liver, pancreas, or small bowel) in the past 6 months or likely within the next 6 months
- Previous episode of sepsis during that hospital admission
- Absolute Neutrophil Count < 500/mm³
- CD4 count < 50/mm³
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 |
|---|---|---|
| EvolocumabAlso: RepathaThree pre-filled shrouded syringes for subcutaneous injection in abdomen. | Drug | High Dose, Low Dose |
| PlaceboAlso: SalinePreservative free 0.9% sodium chloride. Three pre-filled shrouded syringes for subcutaneous injection in abdomen. | Drug | Placebo |
Primary outcome
Area under the plasma LTA and LPS curves
Time frame: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Determine whether evolocumab decreases plasma levels of bacterial LPS and LTA, at 6, 24, 48 and 72 hours, and day 7 by comparing the area under the operating curve between arms.
24 secondary outcomes
Levels of LDL-C
Time frame: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Levels of cytokines IL-6, TNF-alpha and IL-8
Time frame: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)
Concentration of circulating evolocumab and circulating free PCSK9 in septic patients
Time frame: 7 days or less (may be discharged from critical care before day 7)
Cmax of circulating evolocumab and circulating free PCSK9 in septic patients
Time frame: 7 days or less (may be discharged from critical care before day 7)
Days alive
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in 28-day mortality
Time frame: 28 days
Level of organ dysfunction
Time frame: 28 days or less (may be discharged from critical care before day 28)
Level of organ support
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: lactate
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: norepinephrine dose
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: mean arterial pressure
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: heart rate
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: respiratory rate
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: temperature
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: fluid balance
Time frame: 28 days or less (may be discharged from critical care before day 28)
Changes in Vitals: urine output
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: Number of treatment-related adverse events as ranked by severity
Time frame: Day 1 to Day 90
Safety outcomes: changes in blood cell counts
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in coagulation
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in blood analytes
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in urine density
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in urine pH
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: changes in concentration of ketones in urine
Time frame: 28 days or less (may be discharged from critical care before day 28)
Safety outcomes: document other urine abnormalities if required
Time frame: 28 days or less (may be discharged from critical care before day 28)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2020.
- Background: PubMed 28013095Cirstea M, Walley KR, Russell JA, Brunham LR, Genga KR, Boyd JH. Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis. J Crit Care. 2017 Apr;38:289-294. doi: 10.1016/j.jcrc.2016.11.041. Epub 2016 Dec 7.
- Background: PubMed 28317295Roveran Genga K, Lo C, Cirstea M, Zhou G, Walley KR, Russell JA, Levin A, Boyd JH. Two-year follow-up of patients with septic shock presenting with low HDL: the effect upon acute kidney injury, death and estimated glomerular filtration rate. J Intern Med. 2017 May;281(5):518-529. doi: 10.1111/joim.12601. Epub 2017 Mar 19.
- Background: PubMed 11292694Levels JH, Abraham PR, van den Ende A, van Deventer SJ. Distribution and kinetics of lipoprotein-bound endotoxin. Infect Immun. 2001 May;69(5):2821-8. doi: 10.1128/IAI.69.5.2821-2828.2001.
- Background: PubMed 12761109Levels JH, Abraham PR, van Barreveld EP, Meijers JC, van Deventer SJ. Distribution and kinetics of lipoprotein-bound lipoteichoic acid. Infect Immun. 2003 Jun;71(6):3280-4. doi: 10.1128/IAI.71.6.3280-3284.2003.
- Background: PubMed 15784577Levels JH, Marquart JA, Abraham PR, van den Ende AE, Molhuizen HO, van Deventer SJ, Meijers JC. Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun. 2005 Apr;73(4):2321-6. doi: 10.1128/IAI.73.4.2321-2326.2005.
- Background: PubMed 27171436Topchiy E, Cirstea M, Kong HJ, Boyd JH, Wang Y, Russell JA, Walley KR. Lipopolysaccharide Is Cleared from the Circulation by Hepatocytes via the Low Density Lipoprotein Receptor. PLoS One. 2016 May 12;11(5):e0155030. doi: 10.1371/journal.pone.0155030. eCollection 2016.
- Background: PubMed 25320235Walley KR, Thain KR, Russell JA, Reilly MP, Meyer NJ, Ferguson JF, Christie JD, Nakada TA, Fjell CD, Thair SA, Cirstea MS, Boyd JH. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014 Oct 15;6(258):258ra143. doi: 10.1126/scitranslmed.3008782.
- Background: PubMed 26756586Boyd JH, Fjell CD, Russell JA, Sirounis D, Cirstea MS, Walley KR. Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis. J Innate Immun. 2016;8(2):211-20. doi: 10.1159/000442976. Epub 2016 Jan 13.
- Individual participant dataSharing planned: No
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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.
Lynda Lazosky contact
John Boyd, MD principal investigator
University of British Columbia, Providence Health Care
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Evolocumab in people with Sepsis, run by University of British Columbia at 3 sites in Canada.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 3 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Genevieve L Rocheleau (604-682-2344 ext. 64888, grocheleau@providencehealth.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma LTA and LPS curves (time frame: 7 days or less (as data is collected from participants only while they are admitted to critical care, they may be discharged or moved to a different ward before day 7 and therefore subsequent time points would be not be collected)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03869073, which also lists 8 linked publications.
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 3 Mar 2020.