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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
36
Three pre-filled shrouded syringes for subcutaneous injection in abdomen.
Preservative free 0.9% sodium chloride. Three pre-filled shrouded syringes for subcutaneous injection in abdomen.
Surrey Memorial Hospital
Surrey, British Columbia, Canada
NOT_YET_RECRUITINGSt. Paul's Hospital
Vancouver, British Columbia, Canada
RECRUITINGVancouver General Hospital
Vancouver, British Columbia, Canada
NOT_YET_RECRUITINGArea 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.
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 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.
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
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.
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
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.
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Assess the Cmax of circulating evolocumab and free (unbound by antibody) PCSK9 in evolocumab-treated patients with sepsis and compare to placebo controls.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 28 days or less (may be discharged from critical care before day 28)