【摘要】 目的 采用序贯多重分配随机试验（SMART）评价泽泻汤辨治痰湿型良性阵发性位置性眩晕（BPPV）临床有效性及安全性，并评估嵌入式动态治疗策略疗效。方法 采用多中心、前瞻性、序贯多重分配、随机对照试验设计，纳入5个中心的痰湿型BPPV患者225例。第一阶段将患者随机分为试验组150例对照组75例，试验组给予泽泻汤颗粒剂口服，每日2次；对照组给予甲磺酸倍他司汀片（敏使朗）口服，每日1次。连续治疗2周后进行期中分析，眩晕障碍量表（DHI）评分降低值≥15分判定为有效，第二阶段继续接受第一阶段干预方案；DHI评分降低值<15分判定为无效，泽泻汤无效者第二阶段随机使用苓桂术甘汤颗粒剂或泽泻汤加量方颗粒剂，甲磺酸倍他司汀片治疗无效者第二阶段使用泽泻汤颗粒剂，第二阶段共治疗2周。两阶段共构建了3种动态治疗策略，分别为泽泻汤有效继续使用泽泻汤、泽泻汤无效使用苓桂术甘汤（DTR1）；泽泻汤有效继续使用泽泻汤、泽泻汤无效使用泽泻汤加量方（DTR2）；甲磺酸倍他司汀片有效继续使用甲磺酸倍他司汀片、甲磺酸倍他司汀片无效使用泽泻汤（DTR3）。记录患者入组、治疗2周及治疗4周时的DHI评分和痰湿证评分。试验结束后采用加权广义估计方程评价嵌入式动态治疗策略疗效。记录试验全程不良反应发生情况。结果 试验组脱落2例，最终全分析数据（FAS）集共纳入223例受试者进行统计分析。第一、二阶段结束时，试验组与对照组DHI评分及痰湿证评分较治疗前降低（P<0.01），且试验组DHI评分及痰湿证评分均较对照组降低（P<0.05或P<0.01）。第二阶段，泽泻汤有效继续使用泽泻汤83例，甲磺酸倍他司汀片有效继续使用甲磺酸倍他司汀片42例；泽泻汤无效使用苓桂术甘汤组33例，泽泻汤无效使用泽泻汤加量方32例，甲磺酸倍他司汀片无效使用泽泻汤33例。第二阶段整体DHI评分及痰湿证评分较第一阶段整体均降低（P<0.01），提示治疗效果随时间延长而增强。对试验组进一步分析发现，第一阶段与第二阶段DHI评分及痰湿证评分差异均无统计学意义（P>0.05），提示试验组第二阶段的额外效果并不显著。对动态治疗策略进行疗效评价，发现与DTR1和DTR2相比，DTR3的DHI评分及痰湿证评分均明显下降（P<0.01）,DTR1与DTR2之间DHI评分和痰湿证评分差异均无统计学意义（P>0.05）。结论 泽泻汤治疗痰湿型BPPV的整体有效性优于甲磺酸倍他司汀片，两组整体治疗效果均随时间延长而增强，使用甲磺酸倍他司汀片无效者换用泽泻汤可显著改善疗效。更多还原

【Abstract】 Objective To evaluate the clinical efficacy and safety of Zexie Decoction （泽泻汤, ZD） in the syndromedifferentiated treatment of phlegm-dampness-type benign paroxysmal positional vertigo(BPPV) using a sequential multiple assignment randomized trial(SMART), and to assess the effectiveness of embedded dynamic treatment strategies. Methods A multicenter, prospective, sequential multiple assignment randomized controlled trial was conducted, enrolling 225 patients with phlegm-dampness-type BPPV from five centers. In the first stage, patients were randomly assigned to a treatment group with 150 cases or a control group with 75 cases. The treatment group received oral ZD granules twice daily, while the control group received oral betahistine mesilate once daily. After 2 weeks of continuous treatment, an interim analysis was performed. A reduction in the dizziness handicap inventory(DHI) score of ≥15 points was defined as effective, and patients continued the first-stage intervention in the second stage. A DHI reduction of <15 points was defined as ineffective; non-responders in the ZD group were re-randomized in the second stage to receive either Linggui Zhugan Decoction （苓桂术甘汤, LZD） granules or an increased-dose ZD formula, while non-responders in the betahistine group were switched to ZD granules. The second stage lasted an additional 2 weeks. DHI scores and phlegm-dampness syndrome scores were collected at baseline, after 2 weeks, and after 4 weeks of treatment. Three dynamic treatment regimen(DTR) were constructed: continued ZD for responders with switch to LZD for non-responders(DTR1), continued ZD for responders with switch to increased-dose ZD for non-responders(DTR2), and continued betahistine for responders with switch to ZD for non-responders(DTR3). At the end of the trial, weighted generalized estimating equations were used to evaluate the efficacy of the embedded dynamic treatment strategies. Adverse events were recorded throughout the study. Results Two patients in the treatment group dropped out, and a total of 223 participants were included in the final full analysis set. At the end of the first and the second stage, both the treatment group and the control group showed significant reductions in DHI scores and phlegm-dampness syndrome scores(P<0. 01), and compared with the control group, the treatment group exhibited significantly greater reductions in both DHI scores and phlegm-dampness syndrome scores(P<0. 05 or P<0. 01). At the second stage, 83 patients who responded to ZD continued ZD, 42 patients who responded to betahistine continued betahistine, 33 non-responders to ZD received LZD, 32 non-responders to ZD received the increased-dose ZD, and 33 non-responders to betahistine were switched to ZD. Overall DHI scores and phlegm-dampness syndrome scores after the second stage were significantly lower than those after the first stage, indicating that treatment effects increased over time. Further analysis within the treatment group showed no statistically significant differences in overall DHI scores or phlegm-dampness syndrome scores between the first-and second-stage overall effects(P>0. 05), suggesting that the additional effect in the second stage was not significant. Comparative evaluation showed that DTR3 resulted in significantly greater reductions in DHI scores than DTR1 and DTR2(P<0. 01), and significantly greater reductions in phlegm-dampness syndrome scores(P<0. 01). No statistically significant differences were observed between DTR1 and DTR2 in either DHI scores or phlegm-dampness syndrome scores(P>0. 05). Conclusion ZD demonstrates superior overall efficacy compared with betahistine in the treatment of phlegm-dampness-type BPPV. Treatment effects in both groups increased over time, and switching to ZD in patients unresponsive to betahistine significantly improved clinical outcomes.更多还原