Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study
Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study
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DOI：
10.1016/s2468-1253(19)30409-1
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发表时间：
2020-03-01
影响因子：
35.7
通讯作者：
Fang, Jing-Yuan
中科院分区：
文献类型：
--
作者：
Chen, Ying-Xuan;Gao, Qin-Yan;Fang, Jing-Yuan
结直肠腺瘤和结直肠癌的化学预防仍然是一个重要的公共卫生目标。本研究旨在探讨黄连素预防结直肠腺瘤复发的临床潜力和安全性。本研究采用双盲、随机、安慰剂对照试验，在中国6个省的7个医院中心进行。招募了年龄在18-75岁之间的个体，这些个体在招募前6个月内至少有一个但不超过六个组织学证实的结直肠腺瘤，并在招募前6个月内接受了完全息肉切除术，并通过区组随机化（6个区组大小）随机分配（1：1）接受小檗碱（0.3 g，每日两次）或安慰剂片剂。参与者在入组后1年接受第一次随访结肠镜检查，如果没有检测到结直肠腺瘤，则计划在2年时进行第二次随访结肠镜检查。研究持续至最后一名入组受试者达到2年随访点。所有参与者、研究者、内窥镜医生和病理学家均对治疗分配设盲。主要疗效终点为任何随访结肠镜检查时腺瘤复发。分析基于改良的意向治疗，全分析集包括所有接受至少一剂研究药物且具有可用疗效数据的随机化受试者。该研究注册于ClinicalTrials.gov，编号NCT 02226185;试验已经结束，本报告代表最终分析。结果在2014年11月14日至2016年12月30日期间，553名参与者被随机分配到黄连素组，555名参与者被随机分配到安慰剂组。全分析集包括黄连素组429名参与者和安慰剂组462名参与者。在随访期间，发现黄连素组155名（36%）参与者和安慰剂组216名（47%）参与者有复发性腺瘤（复发的未校正相对风险比为0.77，95%CI 0.66-0.91; p=0.001）。随访期间未发现结直肠癌。最常见的不良事件是便秘（黄连素组446例患者中有6例[1%]，
Background Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence.Methods This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0.3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis.Findings Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0.77, 95% CI 0.66-0.91; p=0.001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [