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Abstract：
BACKGROUND: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D.
METHODS: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of \"responders\" in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron.
CONCLUSIONS: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron\'s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond.
BACKGROUND: ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.
METHODS: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of \"responders\" in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron.
CONCLUSIONS: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron\'s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond.
BACKGROUND: ISRCTN, ISRCTN17508514 , Registered on 2 October 2017.
摘要：
背景：腹泻型肠易激综合征（IBS-D）影响高达4%的普通人群。症状包括频繁，松散,或者有急迫性的水汪汪的大便，导致生活质量显著下降，工作效率下降。昂丹司琼,5HT3受体拮抗剂，作为止吐药有超过20年的良好安全记录，尚未广泛用于IBS-D的治疗。它有,然而,被证明可以减缓结肠运输，并且在一个小的随机中，安慰剂对照,交叉试点研究，IBS-D患者受益
方法：本试验为III期，平行组,随机化，双盲,多中心,安慰剂对照试验,进行嵌入式机理研究。符合IBS-D罗马IV标准的参与者（n=400）将从门诊和初级保健诊所以及社交媒体招募，接受昂丹司琼（剂量滴定至每天24mg）或安慰剂12周。在整个审判过程中,参与者将记录他们最严重的腹痛，最紧急的,大便频率,和每天的粪便稠度。主要终点是每组中“响应者”的比例，使用食品和药物管理局（FDA）的建议。次要终点包括疼痛强度，大便稠度，频率,和紧迫性。情绪和生活质量也将被评估。机制评估将包括整个肠道运输，基线和第8周和第11周之间的粪便类胰蛋白酶和粪便胆汁酸浓度。一组参与者还将使用压力调节器进行敏感性评估（n=80），和/或高分辨率结肠测压（n=40），以评估左结肠的运动模式和昂丹司琼的影响。
结论：TRITON试验旨在评估昂丹司琼在多个中心的作用。通过定义昂丹司琼的作用机制，我们希望更好地识别可能有反应的IBS-D患者。
背景：ISRCTN，ISRCTN17508514,2017年10月2日注册。
方法：本试验为III期，平行组,随机化，双盲,多中心,安慰剂对照试验,进行嵌入式机理研究。符合IBS-D罗马IV标准的参与者（n=400）将从门诊和初级保健诊所以及社交媒体招募，接受昂丹司琼（剂量滴定至每天24mg）或安慰剂12周。在整个审判过程中,参与者将记录他们最严重的腹痛，最紧急的,大便频率,和每天的粪便稠度。主要终点是每组中“响应者”的比例，使用食品和药物管理局（FDA）的建议。次要终点包括疼痛强度，大便稠度，频率,和紧迫性。情绪和生活质量也将被评估。机制评估将包括整个肠道运输，基线和第8周和第11周之间的粪便类胰蛋白酶和粪便胆汁酸浓度。一组参与者还将使用压力调节器进行敏感性评估（n=80），和/或高分辨率结肠测压（n=40），以评估左结肠的运动模式和昂丹司琼的影响。
结论：TRITON试验旨在评估昂丹司琼在多个中心的作用。通过定义昂丹司琼的作用机制，我们希望更好地识别可能有反应的IBS-D患者。
背景：ISRCTN，ISRCTN17508514,2017年10月2日注册。
