EAA-Guided AN69-oXiris and PMX-HP Therapy in Septic Patients

Establishing Evidence Based Application of AN69-oXiris and PMX-HP Therapies Based on the Endotoxin Activity Assay in Septic Patients

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.

Inclusion Criteria:

• Participants must meet all of the following criteria:

  1. Adults aged 18 years or older.
  2. Diagnosis of sepsis or septic shock caused by an intra-abdominal infection, including peritonitis, according to the Sepsis-3 criteria.
  3. Completion of emergency surgery for infection source control, with successful surgical control of the infection source.
  4. Admission to the surgical intensive care unit (SICU) for postoperative intensive care.
  5. Ability to undergo measurement of endotoxin activity (EA) using the Endotoxin Activity Assay (EAA).
  6. Determination by a critical care specialist that extracorporeal blood purification therapy with either AN69-oXiris or PMX-HP is clinically indicated.
  7. Ability to obtain central venous access and undergo extracorporeal blood purification therapy.
  8. Provision of voluntary written informed consent by the participant or the participant's legally authorized representative after receiving sufficient information about the study.

Exclusion Criteria:

• Participants meeting any of the following criteria will be excluded:

  1. Younger than 18 years of age.
  2. Surgical source control of the infection was not performed or was considered incomplete.
  3. Pregnant or breastfeeding.
  4. Refusal to participate in the study or inability to obtain informed consent from a legally authorized representative.
  5. Concurrent participation in another clinical study.