摘要Objective:To evaluate the effect and safety of Chinese herbal compound Huashi Tongbi Formula(HTF)for the treatment of erectile dysfunction(ED)with damp heat affecting Pi(Spleen)pattern,and explore the possible mechanisms based on the analysis of gut microbiota.Methods:In this multicentre,randomized,parallel,positive control,noninferiority trial,a total of 162 ED patients with damp heat affecting Pi pattern were randomly divided into a treatment group(108 patients)and a control group(54 patients)in a 2:1 ratio using a random number table method.The treatment group was administered HTF granules(1 bag each time,twice a day).The control group was given sildenafil citrate tablets(50 mg,orally as needed).Both groups were treated for 8 weeks with a 8-week followed-up period.The main indicator was effective rate after 8-week treatment analysed using intention-to-treat(ITT)and per-protocol(PP)methods,and the secondary indicators included International Index of Erectile Function-5(IIEF-5)score,Erectile Quality Score(EQS),and Chinese medicine syndrome(CMS)score,which were analysed using ITT every 2 weeks during 8-week treatment period,and every 4 weeks during 8-week follow-up period.The 16S rDNA sequencing was used to analyse the impact of HTF on the gut microbiota.The adverse events(AEs)and changes in safety indicators of the two groups were recorded.Results:A total of 162 patients were included in the ITT analysis,with 23 patients dropping out during the trial period(12 in the treatment group and 11 in the control group),and 139 patients were included in the PP analysis.ITT and PP analyses revealed that after 8-week treatment the difference and 95％confidence intervals(Cis)in the effective rates between the treatment and the control groups were-3.7％(-17.9％,10.5％)and-4.5％(-18.2％,9.2％),respectively.At 2 weeks of treatment,the treatment group showed lower IIEF-5 and EQS scores but higher CMS score vs.control(P＜0.05);at 4 weeks,IIEF-5 remained lower(P＜0.05),while EQS and CMS scores were comparable(P＞0.05);by 6 weeks,all scores(IIEF-5,EQS,CMS)were similar between groups(P＞0.05);at 8 weeks,IIEF-5 and EQS were comparable,but CMS scores were lower(P＜0.05).During 4-and 8-week follow-up,the treatment group had higher IIEF-5 and EQS scores and lower CMS scores(P＜0.05).Both groups showed significant improvements in all scores from baseline(P＜0.05).There was no significant difference in the safety indicators between groups(P＞0.05).After HTF treatment,the relative abundances of Lachnospiraceae and Blautia increased,contributing the most to the differences in the microbial communities between groups.The abundances of Levilactobacillus and Lactiplantibacillus increased,whereas the abundances of Bilophila,Saccharimonadia,Patescibacteria,and others decreased in the treatment group(linear discriminant analysis score＞2).Nine predictive functions of the gut microbiota including amino acid related enzymes,exosome,mitochondrial biogenesis,etc.were reduced,whereas protein kinase function increased in the treatment group(P＜0.05).Conclusion:HTF showed noninferior efficacy to sildenafil for ED with damp heat affecting Pi pattern,with the advantages of relieving overall symptoms and stable and lasting therapeutic effect after discontinuation,potentially mediated by gut microbiota modulation.(Registration No.ChiCTR2300067825)