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TCIC-001用于结肠镜前肠道准备的有效性和耐受性:一项探索性随机对照临床试验

宋宝回, 庄小龙, 加沙尔·巴合提努尔, 徐晓玥, 徐佳昕, 张丹枫, 钟芸诗, 周平红, 蔡明琰

宋宝回,庄小龙,加沙尔·巴合提努尔,等. TCIC-001用于结肠镜前肠道准备的有效性和耐受性:一项探索性随机对照临床试验[J]. 中国临床医学, xxxx, xx(x): 1-5. DOI: 10.12025/j.issn.1008-6358.2025.20250401
引用本文: 宋宝回,庄小龙,加沙尔·巴合提努尔,等. TCIC-001用于结肠镜前肠道准备的有效性和耐受性:一项探索性随机对照临床试验[J]. 中国临床医学, xxxx, xx(x): 1-5. DOI: 10.12025/j.issn.1008-6358.2025.20250401
SONG B H, ZHUANG X L, BAHETINUER J, et al. Evaluation of efficacy and tolerability of TCIC-001 for bowel preparation prior to colonoscopy: an exploratory randomized controlled clinical trial[J]. Chin J Clin Med, xxxx, xx(x): 1-5. DOI: 10.12025/j.issn.1008-6358.2025.20250401
Citation: SONG B H, ZHUANG X L, BAHETINUER J, et al. Evaluation of efficacy and tolerability of TCIC-001 for bowel preparation prior to colonoscopy: an exploratory randomized controlled clinical trial[J]. Chin J Clin Med, xxxx, xx(x): 1-5. DOI: 10.12025/j.issn.1008-6358.2025.20250401

TCIC-001用于结肠镜前肠道准备的有效性和耐受性:一项探索性随机对照临床试验

基金项目: 

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上海市卫生健康委员会卫生行业临床研究专项 (202340178),2023年度复旦大学附属中山医院临床研究专项基金 (ZSLCYJ202350).

详细信息
    作者简介:

    宋宝回,博士. E-mail:bhsong22@m.fudan.edu.cn

    通讯作者:

    蔡明琰: Tel:021-64041990, E-mail:cai.mingyan@zs-hospital.sh.cn

  • 中图分类号: R 574

Evaluation of efficacy and tolerability of TCIC-001 for bowel preparation prior to colonoscopy: an exploratory randomized controlled clinical trial

Funds: 

Supported by Shanghai Municipal Health Commission Specialized Clinical Research Project (202340178), Clinical Research Special Project of Zhongshan Hospital, Fudan University (ZSLCYJ202350).

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  • 摘要:
    目的 

    比较新型清肠剂TCIC-001与传统聚乙二醇(polyethylene glycol,PEG)电解质散方案在结肠镜检查前肠道准备中的有效性和耐受性。

    方法 

    前瞻性纳入2021年7月至2022年7月复旦大学附属中山医院拟行结肠镜检查的62例患者,随机分为2组。试验组(TCIC-001组,n=31)口服TCIC-001(分阶段饮水,总入液量1 500 mL),对照组(PEG组,n=31)口服PEG(分4次服药,总入液量3 000 mL)。主要终点指标为波士顿评分评估的肠道清洁质量,次要终点指标包括服药依从性、服药时长、排便次数、排便时长、不良事件发生率(电解质紊乱)等。

    结果 

    两组受试者性别、年龄及排便次数差异无统计学意义(P>0.05)。有效性方面,两组受试者各肠段波士顿评分和总分差异均无统计学意义(P>0.05),肠道准备良好率均为93.55%。耐受性方面,TCIC-001组受试者服药时长显著短于PEG组[(48.8±25.9)min vs(82.8±28.4)min,P<0.001],首次排便早于服药完成的发生率明显低于PEG组(9.68% vs 41.94%,P=0.004)。安全性方面,TCIC-001组和PEG组氯离子紊乱发生率(0 vs 9.68%)及钙离子紊乱发生率(3.23% vs 6.45%)差异均无统计学意义。未观察到其他不良事件。

    结论 

    TCIC-001在维持与PEG相当的肠道清洁效果基础上,显著缩短服药时长并提高耐受性,且安全性良好。

    Abstract:
    Objective 

    To compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy.

    Methods 

    A total of 62 patients scheduled for colonoscopy at Zhongshan Hospital, Fudan University, between July 2021 and July 2022 were prospectively selected and randomized divided into 2 groups. The experimental group (TCIC-001 group, n=31) received TCIC-001 (drinked in 2 stages, total fluid intake 1 500 mL), while the control group (PEG group, n=31) received PEG electrolyte powder (administered in 4 doses, total fluid intake 3 000 mL). The primary endpoint was bowel cleanliness assessed by the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included medication compliance, duration of medication completion, defecation frequency, duration of defecation, and adverse events (such as electrolyte disturbances).

    Results 

    No significant differences were observed in sex, age, or defecation frequency between the two groups (P>0.05). For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores (P>0.05). For tolerability, the TCIC-001 group exhibited significantly shorter medication completion time ([48.8±25.9] min vs [82.8±28.4] min, P<0.001) and a lower rate of first defecation before completing medication (9.68% vs 41.94%, P=0.004) than the PEG group. Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%). No other adverse events were observed.

    Conclusions 

    TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

  • 结肠镜检查是早期筛查、诊断、治疗癌前病变和结直肠癌等肠道疾病的标准手段[1]。然而,结直肠病变的检出率高度依赖于肠道清洁程度。20%~40%的患者存在肠道准备不充分的情况,不仅增加腺瘤漏诊率、延长结肠镜操作时间,还会因重复检查导致医疗费用上升[2-3]

    目前,对于拟行结肠镜检查的患者,尚无统一的肠道准备方案。欧洲胃肠内镜学会(European Society of Gastrointestinal Endoscopy,ESGE)指南[4]建议,在便秘患者中应用4 L聚乙二醇(polyethylene glycol,PEG)溶液进行肠道准备。然而,该方案需要患者摄入大量液体,且口感不佳,耐受性较低,5%~15%的患者无法完成肠道准备。口服磷酸钠(OSP)制剂虽然液体摄入量较少,但可能引发水电解质紊乱及严重的肾功能损害,因此不被推荐[5]。《中国消化内镜诊疗相关肠道准备指南》[6]指出,对于便秘等存在肠道准备不充分风险的患者,可采用4 L PEG方案,且在结肠镜检查前3天摄入低渣饮食,或使用促胃肠动力药物等方法。现有肠道准备策略通常需饮用大量液体,患者服药依从性和接受度较差[7]。因此,为改善上述困境,开发一种具有口服液体量小、口感清甜、清肠效果好、不良反应少等优点的肠道准备药物,已成为临床迫切需求。

    TCIC-001为复旦大学附属中山医院内镜中心参与开发的新型肠道准备药物,是从天然植物提取,通过微生物发酵后分离、结晶获得的单糖,属于单一化合物。本研究拟通过探索性临床试验,对比TCIC-001与PEG在结肠镜肠道准备中的有效性和耐受性,为优化肠道准备方案提供新的思路和依据。

    本研究是一项前瞻性、探索性、随机对照研究,已在中国临床试验注册中心注册(注册号:ChiCTR2100048931)。前瞻性纳入2021年7月至2022年7月在复旦大学附属中山医院内镜中心拟行结肠镜检查的患者。纳入标准:(1)年龄18~70周岁;(2)生命体征、体格检查、实验室检查等检查结果正常或异常经研究者判定为无临床意义者;(3)拟住院行结肠镜检查者;(4)能够与研究者进行良好沟通,理解并服从研究要求,在进行任何与研究相关的操作之前理解并自愿签署知情同意书。排除标准:(1)肠道恶性肿瘤患者,疑似肠梗阻的患者;(2)研究前3个月内使用已知对某脏器有损害的药物,严重系统性疾病者或有腹部外科手术史者;(3)妊娠期、哺乳期妇女;(4)实验室检查经研究者判定不符合要求者;(5)研究者认为其他任何可能影响受试者提供知情同意或遵循研究方案的情况(如受试者对研究药物成分过敏、未遵循肠道准备要求或合并使用可能与研究药物发生相互作用非处方药等)。共纳入62例患者,采用随机数字表法分为TCIC-001组(试验组)和PEG组(对照组),每组31例。

    TCIC-001组于结肠镜检查前至少4 h完成给药。将TCIC-001倒入带有刻度的杯中,加入750 mL温水搅拌使之完全溶解,要求受试者在30 min内服用完毕。补充饮用水至饮水总量1 500 mL,并于1 h内饮用完毕。服药后适当走动,并轻揉腹部以加快肠蠕动。

    PEG组于肠镜检查前至少4 h完成给药(A剂+B剂各24袋)。取A剂和B剂各6袋,倒入带有刻度的杯中,加入750 mL温水搅拌至完全溶解,要求受试者30 min内服用完毕。以上配置和服药方法重复3次,在2 h内完成给药,共计饮水总量3 000 mL。每次服药后适当走动,并轻揉腹部以加快肠蠕动。

    主要终点指标为肠道准备情况。采用波士顿评分[8]评估肠道准备质量。分别对右半结肠、横结肠、左半结肠进行评分,总分为3部分肠段评分之和(表1)。总分≥6分且每个肠段评分≥2分被视为肠道准备良好。若未达到以上标准则认为肠道准备差。为保证客观性,每例患者的肠道准备评分均由5 年以上经验的内镜医师以及内镜护士在进镜过程中根据量表条目共同评价,最终结果取两者的平均值。

    表  1  波士顿评分标准
    Table  1.  Boston Bowel Preparation Scale (BBPS)
     Score Criteria
    0 The colon segment is unprepared, and the mucosa is not visible due to solid stool that cannot be cleared.
    1 A portion of the colon mucosa is visible, but other areas are not due to staining and/or residual stool and opaque liquid.
    2 A minor amount of residual staining is observed, along with small fragments of stool and/or opaque liquid. The mucosa of the colon segment is seen well.
    3 The entire mucosa of the colon segment is clearly visible, with no residual staining or small fragments of stool or opaque liquid present.
    下载: 导出CSV 
    | 显示表格

    次要终点指标为服药依从性、排便时长、排便次数、服药时长、首次排便早于服药完成的发生率以及不良事件发生率。服药依从性评估根据患者是否按说明书服药方式在规定时间内完成服药。在肠道准备完成后(结肠镜检查前)采集血样本,评估电解质水平。钠离子正常范围135~145 mmol/L,钾离子正常范围3.5~5.0 mmol/L,氯离子正常范围98~106 mmol/L,钙离子正常范围2.2~2.6 mmol/L。超过或低于正常范围定义为存在电解质紊乱。其余不良事件包括但不限于胃肠道反应、过敏反应、头痛、头晕等。

    采用SPSS 22.0软件进行统计分析。计量资料以$ \bar{x}\pm s $表示,两组间比较采用独立样本t检验;不符合正态分布或方差不齐时采用Mann-Whitney U检验。计数资料以 n(%)表示,分类资料的组间比较采用Fisher确切概率法,等级资料的组间比较采用Wilcoxon秩和检验。检验水准(α)为0.05。

    结果(表2)显示:两组受试者性别、年龄及排便次数差异均无统计学意义。全部患者均按时、按剂量完成服药,服药依从性高。

    表  2  两组受试者基线资料比较
    Table  2.  Comparison of baseline data between the two groups
     Index PEG group (n=31) TCIC-001 group (n=31) P
    Sex n(%) 0.799
     Male 16(51.61) 17(54.84)
     Female 15(48.39) 14(45.16)
    Age/year 56.7±9.3 55.0±10.8 0.520
    Frequency of defecation 7.14±2.03 7.15±1.66 0.980
    下载: 导出CSV 
    | 显示表格

    结果(表3)显示:有效性方面,两组受试者波士顿评分在左半结肠、横结肠、右半结肠的得分及3个肠段总分的差异均无统计学意义(P>0.05)。两组均有29例受试者肠道准备评价结果为“良好”。耐受性方面,TCIC-001组患者服药时长显著短于PEG组[(48.8±25.9)min vs(82.8±28.4)min,P<0.001],排便时长显著久于PEG组[(288.6±74.0)min vs(236.5±74.3)min,P<0.001],首次排便早于服药完成的发生率明显低于PEG组(9.68% vs 41.94%,P=0.004)。

    表  3  两组受试者肠道准备有效性和耐受性比较
    Table  3.  Comparison of efficacy and tolerability for bowel preparation between the two groups
     Index PEG group (n=31) TCIC-001 group (n=31) P
    BBPS
     Left Colon 2.51±0.63 2.58±0.62 0.690
     Transverse Colon 2.52±0.57 2.45±0.62 0.670
     Right Colon 2.29±0.53 2.42±0.56 0.360
     Total score 7.32±1.40 7.45±1.21 0.700
    Bowel preparation evaluation n(%) >0.999
     Good 29(93.55) 29(93.55)
     Poor 2(6.45) 2(6.45)
    Duration of medication/min 82.8±28.4 48.8±25.9 <0.001
    Duration of defecation /min 236.5±74.3 288.6±74.0 0.011
    First defecation before completion of medication n(%) 0.004
     No 18(58.06) 28(90.32)
     Yes 13(41.94) 3(9.68)
      BBPS: Boston Bowel Preparation Scale.
    下载: 导出CSV 
    | 显示表格

    两组受试者均未出现钠离子和钾离子紊乱。PEG组发生3例(9.68%)氯离子紊乱、2例(6.45%)钙离子紊乱,TCIC-001组仅发生1例(3.23%)钙离子紊乱,两组差异无统计学意义。研究期间未观察到任何与药物相关的胃肠道反应、过敏反应、头痛、头晕或其他系统性不良事件。

    结肠镜检查是结直肠癌筛查和早期病变诊断的金标准,其检查质量高度依赖于充分的肠道准备[9]。研究[2-3, 10]表明,肠道准备不充分会增加腺瘤漏诊率、延长操作时间,并增加并发症风险。目前,常规的肠道准备方案如PEG需患者摄入大量液体(3~4 L),常导致腹胀、恶心等不适,影响服药依从性[11-12]。硫酸镁等其他方案虽液体量较少,但存在电解质紊乱风险或口感问题[13]。在临床实践中,依从性差的肠道准备药物不仅影响患者完成度,还可能加重患者的紧张和焦虑情绪,增加肠镜检查失败率。依从性良好的肠道准备药物能够有效缓解患者心理负担,降低结肠镜检查因肠道清洁不充分导致的漏检风险,同时提升内镜操作流程的标准化。

    本研究评估了新型肠道准备药物TCIC-001的耐受性和有效性。结果显示,TCIC-001的液体摄入量为1 500 mL,仅为传统PEG方案的一半,且服药时长显著缩短,患者首次排便早于服药完成的发生率更低。这一结果可能与TCIC-001的分阶段饮水设计有关,TCIC-001组采用“750 mL+后续补液”的分阶段饮水策略,减少单次摄入负荷,降低胃肠道刺激。此外,TCIC-001的配方优化改善了口感,减少恶心、呕吐等不良反应,从而提高患者的耐受性和依从性。有效性方面,TCIC-001的肠道清洁效果与PEG相当,良好率均为93.55%。在安全性方面,TCIC-001表现出良好的电解质平衡,31例患者均未发生氯离子紊乱、仅1例患者发生钙离子紊乱。这表明TCIC-001可降低血容量波动风险,可能适合老年或心肾功能不全患者。与PEG相比,TCIC-001在耐受性上的显著优势(如服药时长缩短、提前排便减少)使其更适合液体不耐受或依从性差的患者群体。

    本研究存在一定局限性:(1)样本量较小的单中心设计,可能限制结果的普适性。(2)未评估TCIC-001的长期安全性,需通过更大规模试验验证其对电解质平衡的远期影响,尤其在高危人群中。未来,课题组将参考专家共识建议,联合祛泡剂(如西甲硅油)或低渣饮食,进一步提升肠道准备质量。

    综上所述,TCIC-001作为一类新型天然来源的单糖化合物,展现出良好的肠道清洁效果,显著提升了患者的耐受性和安全性。其“低液量、分阶段饮水”的设计符合指南对理想肠道准备药物的要求,可能成为便秘患者及特殊人群的更优选择。未来应通过系统药代动力学研究、电解质稳态监测和多中心样本验证,进一步明确其临床优势人群及适应证,并评估其在不同风险患者中的安全性与有效性,为结肠镜前肠道准备提供更优选择。

    伦理声明 本研究于中国临床试验注册中心注册(ChiCTR2100048931 ),获得复旦大学附属中山医院伦理委员会审核批准(B2021-357R),所有参与者知情同意并签署知情同意书。

    利益冲突 所有作者声明不存在利益冲突。

    作者贡献 宋宝回、庄小龙:数据采集、处理,文章撰写;加沙尔·巴合提努尔、徐晓玥、徐佳昕、张丹枫:数据采集、分析;钟芸诗:研究设计、文章修改;周平红、蔡明琰:研究设计、分析,解释数据,文章修订。

  • 表  1   波士顿评分标准

    Table  1   Boston Bowel Preparation Scale (BBPS)

     Score Criteria
    0 The colon segment is unprepared, and the mucosa is not visible due to solid stool that cannot be cleared.
    1 A portion of the colon mucosa is visible, but other areas are not due to staining and/or residual stool and opaque liquid.
    2 A minor amount of residual staining is observed, along with small fragments of stool and/or opaque liquid. The mucosa of the colon segment is seen well.
    3 The entire mucosa of the colon segment is clearly visible, with no residual staining or small fragments of stool or opaque liquid present.
    下载: 导出CSV

    表  2   两组受试者基线资料比较

    Table  2   Comparison of baseline data between the two groups

     Index PEG group (n=31) TCIC-001 group (n=31) P
    Sex n(%) 0.799
     Male 16(51.61) 17(54.84)
     Female 15(48.39) 14(45.16)
    Age/year 56.7±9.3 55.0±10.8 0.520
    Frequency of defecation 7.14±2.03 7.15±1.66 0.980
    下载: 导出CSV

    表  3   两组受试者肠道准备有效性和耐受性比较

    Table  3   Comparison of efficacy and tolerability for bowel preparation between the two groups

     Index PEG group (n=31) TCIC-001 group (n=31) P
    BBPS
     Left Colon 2.51±0.63 2.58±0.62 0.690
     Transverse Colon 2.52±0.57 2.45±0.62 0.670
     Right Colon 2.29±0.53 2.42±0.56 0.360
     Total score 7.32±1.40 7.45±1.21 0.700
    Bowel preparation evaluation n(%) >0.999
     Good 29(93.55) 29(93.55)
     Poor 2(6.45) 2(6.45)
    Duration of medication/min 82.8±28.4 48.8±25.9 <0.001
    Duration of defecation /min 236.5±74.3 288.6±74.0 0.011
    First defecation before completion of medication n(%) 0.004
     No 18(58.06) 28(90.32)
     Yes 13(41.94) 3(9.68)
      BBPS: Boston Bowel Preparation Scale.
    下载: 导出CSV
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    [6] 中国医师协会内镜医师分会消化内镜专业委员会, 中国抗癌协会肿瘤内镜学专业委员会. 中国消化内镜诊疗相关肠道准备指南(2019, 上海)[J]. 中华消化内镜杂志, 2019, 36(7): 457-469. DOI: 10.3760/cma.j.issn.1007-5232.2019.07.001

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    REUMKENS A, VAN DER ZANDER Q, WINKENS B, et al. Electrolyte disturbances after bowel preparation for colonoscopy: systematic review and meta-analysis[J]. Dig Endosc, 2022, 34(5): 913-926. DOI: 10.1111/den.14237

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    ALI I A, ROTON D, MADHOUN M. Oral sulfate solution versus low-volume polyethylene glycol for bowel preparation: meta-analysis of randomized controlled trials[J]. Dig Endosc, 2022, 34(4): 721-728. DOI: 10.1111/den.14194

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出版历程
  • 收稿日期:  2025-03-30
  • 录用日期:  2025-05-04
  • 网络出版日期:  2025-06-19

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