Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan
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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.
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).
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).
Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients.
KeywordsHeartburn Abdominal discomfort Rikkunshito Acid-suppressive therapy
We are grateful to the GERD 4 Study Group, as listed below, for their contribution to this study. The GERD 4 Study Group: Shiroishi Kyoritsu Hospital, Kinoshita Clinic, Takashima Hospital, Nagae Pediatric Medicine Clinic, Arita Kyoritsu Hospital, Hiramatsu Hospital, Fujise Clinic, Imamura Clinic, Oda Regional Medical Center, Saga Prefectural Hospital Kouseikan, Jinnouchi Gastrointestinal and Internal Medicine, Kanzaki Clinic in Saga, Sousei Hospital, Taisyo Hospital, Osaka Saiseikai Nakatsu Hospital, Hoshigaoka Koseinenkin Hospital, Osaka City Juso Hospital, and Izumiotsu Municipal Hospital (all in Osaka, Japan).
Conflict of interest
- 8.Futagami S, Iwakiri K, Shindo T, Kawagoe T, Horie A, Shimpuku M, et al. The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying. J Gastroenterol. 2010;45:413–21.PubMedCrossRefGoogle Scholar
- 12.Tominaga K, Kido T, Ochi M, Sadakane C, Mase A, Okazaki H, et al. The traditional Japanese medicine rikkunshito promotes gastric emptying via the antagonistic action of the 5-HT3 receptor pathway in rats. eCAM 2009:1–8. doi: 10.1093/ecam/nep173.
- 13.Hattori T, Fujitsuka N, Asakawa A, Inui A. A strategy using rikkunshito (Liu-Jun-Zi-Tang), a Japanese traditional medicine, to treat gastrointestinal disease. In: Satoh H, editor. Basics of evidences-based herbal medicine. Kerala: Research Signpost; 2010. p. 149–60.Google Scholar
- 16.Pehlivanov N, Liu J, Mittal R. Sustained esophageal contraction: a motor correlate of heartburn symptom. Am J Gastroenterol. 2001;281:743–51.Google Scholar
- 25.Tomono H, Ito Y, Watanabe T. Successful antiemetics treatment of TSUMURA rikkunshito extract granules for ethical use in addition to other antiemetics agents in neoadjuvant chemotherapy for an advanced breast cancer patient (in Japanese with English abstract). Jpn J Cancer Chemother. 2006;33:1129–31.Google Scholar
- 32.Kim YS, Kim TH, Choi CS, Shon YW, Kim SW, Seo GS, et al. Effect of itopride, a new prokinetic, in patients with mild GERD: A pilot study. World J Gastroenterol. 2005;22:4210–4.Google Scholar
- 33.Miwa H, Koseki J, Oshima T, Kondo T, Tomita T, Watari J, et al. Rikkunshito, a traditional Japanese medicine, may relieve abdominal symptoms in rats with experimental esophagitis by improving the barrier function of epithelial cells in esophageal mucosa. J Gastroenterol. 2010;45:478–87.PubMedCrossRefGoogle Scholar