Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia—a multicenter, double‐blind, randomized, placebo‐controlled study

• Published in: Neurogastroenterology and motility 2014-07, Vol.26 (7), p.950-961
• Main Authors: Suzuki, H., Matsuzaki, J., Fukushima, Y., Suzaki, F., Kasugai, K., Nishizawa, T., Naito, Y., Hayakawa, T., Kamiya, T., Andoh, T., Yoshida, H., Tokura, Y., Nagata, H., Kobayakawa, M., Mori, M., Kato, K., Hosoda, H., Takebayashi, T., Miura, S., Uemura, N., Joh, T., Hibi, T., Tack, J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Double-Blind Method; Drugs, Chinese Herbal - therapeutic use; Dyspepsia - blood; Dyspepsia - drug therapy; epigastric pain; Female; functional dyspepsia; Ghrelin - blood; Helicobacter; Helicobacter pylori; Humans; Male; Middle Aged; Pain - drug therapy; Pain Measurement; postprandial fullness; rikkunshito; Treatment Outcome; Young Adult
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.12348

Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large‐scale, randomized, placebo‐controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo‐controlled, parallel‐group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty‐seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori‐infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori‐uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori‐positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954). This study aimed to determine the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for treating functional dyspepsia. The proportion of responders (GPA scores) and the proportion of participants with individual symptom relief (5‐point Likert scales) were compared between the rikkunshito and placebo groups by using the Fisher's exact test. Administration of rikkunshito for 8 weeks reduced dyspepsia (Responder rates: rikkunshito, 33.6%; placebo, 23.8%; p = 0.09), particularly symptoms of epigastric pain (rikkunshito, 44.0%; placebo 30.3%; p = 0.04) and postprandial fullness (rikkunshito, 50.4%; placebo 37.7%; p = 0.06). Weekly changes in these parameters in the two