Sepsis and septic shock are life-threatening conditions in which the body's response to infection can cause dangerously low blood pressure and organ failure. In some patients with an infection inside the abdomen, severe inflammation may continue even after emergency surgery or another procedure has controlled the source of infection. Endotoxin is a substance produced by certain bacteria that may worsen this inflammation. The Endotoxin Activity Assay is a blood test that estimates how strongly endotoxin is affecting the body. This study will compare two blood purification treatments, AN69-oXiris and polymyxin B hemoperfusion (PMX-HP), in patients receiving intensive care for sepsis or septic shock caused by an intra-abdominal infection. Blood purification removes blood through a central venous catheter, passes it through a special filter or cartridge, and then returns it to the body. These treatments are intended to reduce endotoxin or other substances involved in inflammation. The study plans to enroll 50 participants at Seoul St. Mary's Hospital. Participants will be assigned by chance, in a 1:1 ratio, to receive either AN69-oXiris or PMX-HP. Participants and the clinical team will know which treatment is used.
This is a prospective, randomized, open-label, active-comparator study evaluating patients who require intensive care for sepsis or septic shock related to an intra-abdominal infection, including patients who have undergone emergency surgery or another procedure for infection source control. After written informed consent and confirmation of eligibility, participants will be randomized in a 1:1 ratio to AN69-oXiris-based blood purification or PMX-HP. Because the devices and treatment procedures are visibly different, treatment allocation will not be blinded. In the AN69-oXiris group, blood will be circulated through an AN69-oXiris filter using an extracorporeal blood purification system during sequential treatment cycles over the 72-hour study period. In the PMX-HP group, blood will be circulated through a polymyxin B-immobilized cartridge for one or two hemoperfusion sessions, with the second session occurring approximately 24 hours after treatment initiation when administered. Both treatments will be delivered through a central venous catheter with standard intensive care monitoring. Standard treatment for sepsis and septic shock, including infection source control, antimicrobial therapy, hemodynamic support, organ support, and other treatment considered necessary by the attending clinicians, will continue according to each participant's clinical condition. Endotoxin activity will be assessed using the Endotoxin Activity Assay before and after blood purification. Clinical and laboratory assessments will be performed at prespecified time points from baseline through 72 hours. These assessments will include blood pressure, vasopressor dose, lactate level, inflammatory markers, complete blood count, blood urea nitrogen and creatinine, C-reactive protein, procalcitonin, arterial blood gas measurements, and measures of organ function. Additional clinical outcomes will include complications, intensive care unit and hospital length of stay, and mortality. The study will compare changes in endotoxin activity and clinical response between the two treatment groups and will examine whether baseline endotoxin activity and illness severity are associated with differential treatment response. The investigators hypothesize that integrating endotoxin activity with short-term physiologic and organ-function changes may help identify which blood purification strategy is more appropriate for specific patients. Study treatment may be discontinued or modified if a participant's condition worsens or if the attending medical team determines that continued treatment is not appropriate. Necessary standard intensive care treatment will be maintained regardless of discontinuation or modification of the assigned study treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DEVICE_FEASIBILITY
Masking
DOUBLE
Enrollment
50
Participants assigned to the AN69-oXiris group will receive extracorporeal blood purification using an AN69-oXiris adsorptive hemofilter connected to a Prismaflex continuous renal replacement therapy system. Vascular access will be obtained using a 12-Fr dual-lumen catheter inserted into the internal jugular or femoral vein. Treatment will begin within 12 hours after successful surgical source control. One filter will be used per session for three consecutive 24-hour sessions, with a maximum treatment duration of 72 hours. The blood flow rate will be 100-150 mL/min, the replacement fluid rate will be 150-900 mL/hour, and the dialysate flow rate will be 700-1,200 mL/hour. Treatment settings may be adjusted according to the participant's clinical condition. Standard treatment for sepsis and septic shock will be provided concurrently.
Participants assigned to the PMX-HP group will receive direct hemoperfusion using a PMX-20R cartridge containing polymyxin B-immobilized fibers connected to a Prismaflex extracorporeal circulation system. Vascular access will be obtained using a 12-Fr central venous catheter inserted into the internal jugular or femoral vein. The first session will begin within 12 hours after successful surgical source control, and the second session will be performed within 24 hours after completion of the first session. One cartridge will be used per session for a total of two 6-hour sessions. The blood flow rate will be 80-120 mL/min and may be adjusted according to the participant's clinical condition. Treatment may be discontinued early if clinically necessary. Standard treatment for sepsis and septic shock will be provided concurrently.
Division of Trauma and Surgical Critical Care, Department of Surgery, Seoul St. Mary's Hospital, Seoul, Seocho-gu, Banpo-dong banpodaero 222
Seoul, South Korea
Change in Endotoxin Activity Measured by the Endotoxin Activity Assay From Baseline Through 72 Hours
Endotoxin activity (EA) will be measured using the Endotoxin Activity Assay (EAA) at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Higher EA values indicate greater endotoxin activity. For each post-baseline time point, the change from baseline will be calculated as the EA value at T1, T2, or T3 minus the EA value at T0. A negative change indicates a reduction in endotoxin activity. Changes in EA values over time will be compared between the AN69-oXiris and PMX-HP groups.
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
28-day mortality rate
Proportion of patients who died within 28 days after surgery among participants
Time frame: Participants were followed up to 28 days immediately after the surgery
Intensive Care Unit Length of Stay
Intensive care unit length of stay will be calculated as the number of days from intensive care unit admission to intensive care unit discharge. Participants who die before intensive care unit discharge will be accounted for according to the prespecified statistical analysis plan. The outcome will be compared between the two treatment groups.
Time frame: From intensive care unit admission to intensive care unit discharge or in-hospital death, assessed up to 180 days.
Hospital Length of Stay
Hospital length of stay will be calculated as the number of days from hospital admission to hospital discharge. Participants who die before hospital discharge will be accounted for according to the prespecified statistical analysis plan. The outcome will be compared between the two treatment groups.
Time frame: From hospital admission until hospital discharge or in-hospital death, whichever occurs first, assessed up to 180 days.
Incidence of Postoperative Complications
The proportion of participants who experience one or more protocol-defined postoperative complications following the index surgery will be assessed. Complications will be identified from medical records and investigator assessments and compared between the AN69-oXiris and PMX-HP groups.
Time frame: From the index surgery through hospital discharge, assessed up to 180 days after surgery. For participants discharged before 180 days without postoperative complications, events occurring after hospital discharge will not be assessed.
Change in Sequential Organ Failure Assessment (SOFA) Score From Baseline Through 72 Hours
The SOFA score assesses dysfunction in six organ systems: respiratory, coagulation, hepatic, cardiovascular, central nervous system, and renal. The total score ranges from 0 to 24, with higher scores indicating more severe organ dysfunction. Change from baseline will be calculated as the score at T1, T2, or T3 minus the score at T0. A negative change indicates improvement. Changes over time will be compared between the two treatment groups.
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Treatment Cost per Participant Alive at Day 28
Direct costs attributable to the assigned blood purification treatment, including the costs of filters or cartridges and treatment-related consumable supplies, will be calculated in Korean won. Treatment costs will be analyzed in relation to survival status at Day 28. Cost-effectiveness will be expressed as the treatment cost per participant alive at Day 28 and compared between the AN69-oXiris and PMX-HP groups according to the prespecified analysis plan.
Time frame: Treatment costs accrued from treatment initiation through completion of the assigned treatment, with survival assessed at Day 28
Change in C-Reactive Protein From Baseline Through 72 Hours
C-reactive protein (CRP) will be measured at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Change from baseline at each post-treatment time point will be calculated as the CRP value at T1, T2, or T3 minus the value at T0. Changes over time will be compared between the AN69-oXiris and PMX-HP groups. Unit of Measure: mg/L
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Change in Procalcitonin From Baseline Through 72 Hours
Procalcitonin (PCT) will be measured at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Change from baseline at each post-treatment time point will be calculated as the PCT value at T1, T2, or T3 minus the value at T0. Changes over time will be compared between the AN69-oXiris and PMX-HP groups. Unit of Measure: ng/mL
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Change in Presepsin From Baseline Through 72 Hours
Presepsin will be measured at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Change from baseline at each post-treatment time point will be calculated as the presepsin value at T1, T2, or T3 minus the value at T0. Changes over time will be compared between the AN69-oXiris and PMX-HP groups. Unit of Measure: pg/mL
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Change in Lactate From Baseline Through 72 Hours
Blood lactate will be measured at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Change from baseline at each post-treatment time point will be calculated as the lactate value at T1, T2, or T3 minus the value at T0. Changes over time will be compared between the AN69-oXiris and PMX-HP groups. Unit of Measure: mmol/L
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Change in Blood Urea Nitrogen and Serum Creatinine From Baseline Through 72 Hours
Blood urea nitrogen (BUN) and serum creatinine(Cr) will be measured at baseline (T0) and at 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment. Change from baseline at each post-treatment time point will be calculated as the BUN and Cr value at T1, T2, or T3 minus the value at T0. Changes over time will be compared between the AN69-oXiris and PMX-HP groups. Unit of Measure: mg/dL
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
Weight-Normalized Urine Output Through 72 Hours
Urine output will be recorded during the protocol-defined assessment intervals and normalized by body weight. Weight-normalized urine output will be compared between the AN69-oXiris and PMX-HP groups at each assessment interval. Unit of Measure: mL/kg/hour
Time frame: Baseline (T0) and 24 hours (T1), 48 hours (T2), and 72 hours (T3) after initiation of the assigned treatment
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