Lipopolysaccharide Adsorption (Efferon LPS) in Patients With Ulcerative Colitis and Crohn Disease

Official title

A Randomized Pilot Study of LPS Adsorption Using the Efferon LPS Device in Patients With Ulcerative Colitis and Crohn's Disease During Disease Exacerbation

Overview

The goal of the study is to evaluate the safety and efficacy of multimodal (cytokine and lipopolysaccharide) hemoperfusion using the Efferon® LPS device in patients with ulcerative colitis and Crohn disease. Participants will be assigned to two groups for comparison: a control group receiving baseline therapy and a treatment group receiving baseline therapy in combination with Efferon® LPS hemoadsorption.

Detailed description

Inflammatory bowel diseases (IBD) represent a group of chronic inflammatory disorders, with the main clinical entities being Crohn's disease and ulcerative colitis. The prevalence of IBD is increasing worldwide, imposing a substantial socioeconomic burden on society and healthcare systems.In IBD, in the presence of predisposing genetic factors and unclear triggers, a loss of immunological tolerance to luminal antigens occurs. This results in persistent inflammation of the intestinal wall, leading to mucosal damage and increased permeability of the mucosa to various antigens, which further amplify and sustain the pro-inflammatory immune response. Increased intestinal permeability and subsequent endotoxin translocation may also play a role in the pathogenesis of IBD.

Currently used treatments for IBD aim to control inflammation and modulate mucosal immune responses by blocking cytokine activity, such as tumor necrosis factor (TNF) and Interleukin 23, preventing the homing of immune cells to the gut, or inhibiting T-cell egress from lymph nodes.Steroid-free remission, due to the adverse effects associated with corticosteroids, is one of the primary treatment goals in IBD, whereas long-term corticosteroid use is considered a marker of suboptimal disease control.

Some patients with highly active IBD, who cannot be treated with pharmacological therapy for various reasons (including refractoriness, intolerance, or significant adverse effects), require alternative treatment approaches. Among these, extracorporeal therapy modalities, which have been rapidly developing in recent years, represent a promising therapeutic option.

Compared with standard steroid therapy, extracorporeal treatment modalities demonstrate comparable therapeutic efficacy and safety. In addition, extracorporeal therapies may represent an alternative treatment option for IBD without the undesirable adverse effects associated with systemic corticosteroids, immunosuppressants, and biologic agents. This also applies to hemoadsorption, which has been shown to reduce circulating levels of cytokines, various cytotoxins, myoglobin, and products of cellular breakdown in patients' blood. However, data on the use of cytokine hemoadsorption in IBD are extremely limited, and no published studies have been identified regarding the use of lipopolysaccharide (endotoxin) adsorption in IBD.

The Efferon® LPS device was originally developed for use in sepsis, leveraging its ability to effectively target both primary and secondary inflammatory mediators. This therapeutic approach also holds substantial potential for the treatment of other pathological conditions characterized by complex inflammatory responses.

This study aims to evaluate the safety and efficacy of multimodal (cytokine and lipopolysaccharide) hemoperfusion using the Efferon® LPS device in patients with ulcerative colitis and Crohn Disease.

Interventions

• Device Efferon LPS
  Efferon LPS, a medical device, which is a single-use cartridge filled with a polymeric adsorbent that selectively adsorbs endotoxin via surface-immobilized ligand and excessive cytokines via its intrinsic porosity. Hemoadsorption was administered in 3-4 sessions of at least 2 hours each via peripheral vascular access, with intervals of no more than 5 days between sessions.

Primary outcome measures

• Change in the Crohn's Disease Activity Index (CDAI) score [Time frame: 1-90 days]
• Change in the Mayo score in patients with ulcerative colitis [Time frame: 1-90 days]

Secondary outcome measures (4)

• Change in the Simple Endoscopic Score for Crohn's Disease (SES-CD) [Time frame: 1-90 days]
• Change in the Endoscopic Activity Index for Ulcerative Colitis (Schroeder Score) [Time frame: 1-90 days]
• Hospital length of stay [Time frame: 1-90 days]
• The Inflammatory Bowel Disease Questionnaire (IBDQ) index [Time frame: 1-90 days]

Eligibility criteria

Inclusion criteria

• Crohn's disease (ICD-10: K50), extensive disease, with a chronic continuous or relapsing course during an exacerbation (flare), including:

• Severe flare: CDAI ≥ 450 and/or SES-CD > 15;
• Moderate flare: CDAI 350-450 and/or SES-CD > 7, steroid-refractory.
• Ulcerative colitis (ICD-10: K51), with a chronic continuous or relapsing course during an exacerbation (flare), including:

• Severe flare: Mayo score ≥ 10 and partial Mayo score ≥ 6;
• Moderate flare: Mayo score 6-9 and partial Mayo score ≥ 3, steroid-refractory or steroid-dependent.
• Presence of signs and symptoms of ulcerative colitis or Crohn's disease for at least 3 months prior to study enrollment.
• The diagnosis must be confirmed by clinical and endoscopic findings and supported by a histopathology report
• The patient's condition allows Efferon LPS therapy to be performed for at least 2 hours

Exclusion criteria

• Indeterminate colitis, radiation colitis, ischemic colitis,confirmed presence of megacolon, strictures, or stenosis causing symptoms of intestinal obstruction.
• Expected need for bowel resection within 4 weeks after enrollment
• Presence at hospitalization of a stoma, ileal pouch-anal anastomosis, or a fistula with purulent discharge (which, in the investigator's opinion, is likely to require surgical or medical intervention within 4 weeks after enrollment), or planned ileostomy or colostomy.
• Partial or total colectomy, small bowel resection, or creation of a stoma (i.e., temporary or permanent colostomy, ileostomy, or other enterostomy) within 6 months prior to enrollment, or presence of an external or entero-enteric fistula with symptoms within 6 months prior to enrollment.
• Suspected or diagnosed intra-abdominal or perianal abscess that has not been adequately treated.
• Positive test for Clostridioides difficile toxin.
• Positive test for infectious pathogens (including helminth eggs, parasites, or bacterial infections).
• History of malignancy within the past 5 years, including solid tumors or hematologic malignancies (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin in situ, or cervical dysplasia/cancer that has been surgically excised with complete resolution), or colonic mucosal dysplasia that has not been completely removed.
• End-stage renal disease.
• Acute pulmonary embolism confirmed by imaging.
• Acute myocardial infarction within the last 4 weeks.
• Acute cerebrovascular accident (stroke) within the last 8 weeks.
• Dementia.
• Uncontrolled bleeding (acute blood loss within the last 24 hours).
• History or current evidence of recurrent or chronic viral infection (e.g., hepatitis B virus, hepatitis C virus, or human immunodeficiency virus \[HIV\]).
• Alcohol or drug dependence.
• Any other condition that, in the investigator's opinion, would preclude the patient's participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 1 center

• North-Western State Medical University named after I.I. Mechnikov — Saint Petersburg

Identifiers

NCT: NCT07383597 · efferon-lps-2025-04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗