Objective

2

To evaluate the clinical efficacy and safety of

Zexie Decoction

（泽泻汤， ZD） in the syndrome-differentiated treatment of phlegm-dampness-type benign paroxysmal positional vertigo （BPPV） using a sequential multiple assignment randomized trial （SMART）， and to assess the effecti

veness of embedded dynamic treatment strategies.

Methods

2

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

2

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

2

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.