A Randomized Pilot Study of LPS Adsorption Using the Efferon LPS Device in Patients With Ulcerative Colitis and Crohn's Disease During Disease Exacerbation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in the Crohn's Disease Activity Index (CDAI) score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Baseline therapy
These patients will receive standard therapy for Crohn disease or ulcerative colitis
Baseline therapy + Efferon LPS
These patients will receive standard therapy for Crohn disease or ulcerative colitis and Efferon LPS hemoadsorption.
干预措施: Efferon LPS (Device)
结局指标
主要结局
Change in the Crohn's Disease Activity Index (CDAI) score
时间窗: 1-90 days
The Crohn's Disease Activity Index (CDAI) is calculated as a composite score based on a set of clinical and laboratory parameters reflecting disease activity. The higher the CDAI score, the greater the clinical activity of Crohn's disease. A CDAI score below 150 corresponds to clinical remission, scores of 150-300 indicate mild disease activity, 301-450 indicate moderate disease activity and a score of 450 points or higher is considered indicative of a severe disease flare.
Change in the Mayo score in patients with ulcerative colitis
时间窗: 1-90 days
The Mayo score is a composite index used to assess disease activity in ulcerative colitis. It includes four components evaluating stool frequency, rectal bleeding, endoscopic findings, and the physician's global assessment. Higher Mayo scores indicate greater severity of ulcerative colitis. Disease activity can be categorized based on the total Mayo score as follows: 0-2 points indicate remission, 3-5 points indicate mild disease, 6-9 points indicate moderate disease, and 10-12 points indicate severe disease.
次要结局
- Change in the Simple Endoscopic Score for Crohn's Disease (SES-CD)(1-90 days)
- Change in the Endoscopic Activity Index for Ulcerative Colitis (Schroeder Score)(1-90 days)
- Hospital length of stay(1-90 days)
- The Inflammatory Bowel Disease Questionnaire (IBDQ) index(1-90 days)