title: Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan.
abstract: BACKGROUND
  To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients.
  
  
  METHODS
  One hundred and four patients with GERD symptoms remaining after 4-week treatment with RPZ (10 mg/day) were randomly assigned to 4 weeks of either combination therapy [rikkunshito (7.5 g/day) with a standard dose of RPZ (10 mg/day)] or a double dose of RPZ (20 mg/day). The primary endpoint was the improvement rate, calculated based on the frequency scale for the symptoms of GERD (FSSG) before and after treatment. Subgroup analysis was also performed with respect to each subject's background factors such as reflux esophagitis (RE)/non-erosive GERD (NERD), age, gender, and body mass index (BMI).
  
  
  RESULTS
  Four-week treatment with rikkunshito combined with RPZ significantly decreased the FSSG score from 17.6 ± 6.5 to 12.0 ± 6.9, similar to the decrease seen on treatment with a double dose of RPZ. Regarding the therapeutic improvement rate, there were also significant effects in both groups. However, in the subgroup analysis based on RE/NERD, the improvement rate of male NERD patients in the rikkunshito group was significantly greater than that of such patients in the other group (P < 0.05). In the rikkunshito group, the treatment was more effective in NERD patients with a low BMI than in those with a high BMI (P < 0.05).
  
  
  CONCLUSIONS
  Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, Japan. tomy@med.osaka-cu.ac.jp
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Mio
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shimoyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Umegaki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Kusano
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064750:Rabeprazole; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004365:Drugs, Chinese Herbal; D054328:Proton Pump Inhibitors; C084136:liu-jun-zi-tang; D064750:Rabeprazole
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