The Effect of Oral Clostridium Butyricum on the Recurrence After Colonoscopic Resection of Colorectal Adenoma - A Multicenter, Double-blinded, Differential Design, Randomized, Placebo-controlled Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 294
- 试验地点
- 2
- 主要终点
- The 3-year cumulative recurrence rate of CRA
研究概览
简要总结
The prevention of recurrence after colorectal adenoma resection remains an urgent medical issue to be addressed. Previous studies have mainly focused on nonsteroidal anti-inflammatory drugs, calcium supplements, and vitamins. The gut microbiota and its metabolic products are believed to play a potential role in the development and progression of colorectal adenomas. Clostridium butyricum, a butyrate-producing probiotic, has not yet been studied for its potential in preventing the recurrence of colorectal adenomas following resection. Therefore, this study, designed as a multicenter, double-blind, placebo-controlled randomized controlled trial, aims to explore evidence-based data on the role of Clostridium butyricum in preventing colorectal adenoma recurrence.
详细描述
Statistical Analysis Plan the intention-to-treat (ITT) population (all randomized participants analyzed according to the randomized assignment)-the primary analysis set; the per-protocol (PP) population (participants with ≥80% treatment compliance and no major protocol violations)-used for confirmatory efficacy consistency testing; and the safety analysis (SA) population (all randomized participants exposed to the investigational product or placebo with post-intervention safety data)-used for all safety evaluations.
Primary Outcome Analysis Due to the asymptomatic nature of colorectal adenoma recurrence, which can only be detected at scheduled annual colonoscopic examinations, the time to recurrence is considered interval-censored data (i.e., the exact recurrence time is unknown, only that it occurred within a 12-month window between two consecutive colonoscopies). Given this data characteristic, the 3-year cumulative CRA recurrence rate will be estimated using the life table method, which divides follow-up time into 12-month intervals (0-12, 12-24, 24-36 months). Between-group comparisons of recurrence-free survival will be performed using the stratified log-rank test (stratified by participating center). Hazard ratios (HR) and corresponding 95% confidence intervals (CIs) will be estimated using a stratified Cox proportional hazards model. To ensure the robustness of the findings, sensitivity analyses using the Turnbull algorithm (an extension of the Kaplan-Meier method for interval-censored data) will also be conducted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 years
- •No restriction on sex
- •Boston Bowel Preparation Score (BBPS) ≥ 7 prior to endoscopic procedure
- •Completed endoscopic resection of colorectal adenomas (including cold snare polypectomy, ESD, EMR, etc.) with no residual adenomas or polyps observed endoscopically
- •Histologically confirmed adenomas (including tubular, villous, or tubulovillous types) without malignant transformation
- •Able to take oral medication
- •Signed informed consent
排除标准
- •Use of probiotics, prebiotics, synbiotics, or antibiotics within 2 weeks prior to enrollment
- •Presence of psychiatric disorders or other conditions preventing compliance with the intervention
- •Dysfunction of vital organs (liver, kidney, heart, etc.) deemed unsuitable for clinical study participation after evaluation
- •Participation in other clinical trials within 3 months prior to enrollment
- •History of gastrointestinal surgery (excluding endoscopic procedures)
- •History of inflammatory bowel disease
- •History of autoimmune diseases
- •Long-term use of aspirin (≥100 mg/day for over 3 months) or calcium supplements (≥1200 mg/day for over 3 months)
- •Pregnancy or breastfeeding
- •Previous treatment for colorectal adenomas (including endoscopic or surgical resection)
- •Familial adenomatous polyposis (FAP)
研究组 & 干预措施
Clostridium butyricum group
Oral Clostridium butyricum capsules, Live: take 3 capsules twice daily (bid) for the first 3 months after adenoma resection, then continue with 3 capsules once daily (qd) until 3 years post-resection (each capsule contains ≥6.3 × 10⁶ CFU of Clostridium butyricum).
干预措施: Clostridium butyricum capsules, Live (Drug)
Placebo group
Placebo capsules containing corn starch, with identical appearance, weight, and administration method as the study group.
干预措施: Control (placebo) (Other)
结局指标
主要结局
The 3-year cumulative recurrence rate of CRA
时间窗: 3 years
The 3-year cumulative recurrence rate of CRA following colonoscopic resection. Recurrence is defined as the identification of new or residual adenomatous polyps in the colorectum on colonoscopy during the follow-up period, confirmed pathologically.
3-year adenoma recurrence rate
时间窗: 3 years
Each subject will undergo a colonoscopy once per year after enrollment to monitor for adenoma recurrence. The 3-year recurrence rate is calculated as: 3-year recurrence rate (%) = (Number of subjects with adenoma recurrence / Total number of subjects) × 100%
次要结局
- 1-year and 2 year adenoma recurrence rate(1-year and 2-year after enrollment)
- adenoma burden(Assessed at 12, 24, and 36 months post-enrollment)
- 1-year adenoma recurrence rate(1-year after enrollment)
- incidence of colorectal cancer(3 years after enrollment)
- Incidence of advanced colorectal adenomas(3 years after enrollment)
- Location of adenoma recurrence(3 years)
- Number of recurrent adenomas(3 years)
- Histological classification of recurrent adenomas(3 years)
- Size of recurrent adenomas(3 years)
研究者
Zhou Yanbing
The Director of the Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University
The Affiliated Hospital of Qingdao University