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Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors

Usual dose proton pump inhibitors plus hangeshashinto versus double-dose proton pump inhibitors: randomized, multicenter open label exploratory study

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Abstract

Background

Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) leads to a clinical decline in the quality of life (QOL). Therefore, new treatment options are needed. We performed a multicenter, randomized, parallel-group exploratory trial to determine the efficacy of hangeshashinto (HST) in patients with PPI-refractory GERD.

Methods

We enrolled 78 patients with PPI-refractory GERD for standard PPI regimens for at least 4 weeks and randomly assigned patients to receive either a combination of usual dose of rabeprazole (10 mg/day) + HST (7.5 g/day; HST group) or a double dose of rabeprazole (20 mg/day; double-dose PPI group). The primary end points were the extent of improvement in FSSG (Frequency Scale for the Symptoms of GERD) score and the change over time in FSSG score.

Results

There was no significant difference in terms of the improvement degree of the FSSG score between the two groups. Although the total FSSG score and reflux syndrome score decreased significantly for both groups over time (p < 0.001), the acid-related dyspepsia (ARD) score decreased significantly in the HST group from 1 week after drug administration (p < 0.05), indicating an improvement in the condition earlier than in the double-dose PPI group. Moreover, in examinations concerning BMI and age, the HST group had a significantly higher improvement degree of ARD score in patients with BMI < 22 (p < 0.05) and aged < 65 years (p < 0.05) than the double-dose PPI group.

Conclusions

HST may be beneficial for patients with PPI-refractory GERD, particularly in non-obese and non-elderly patients with dyspepsia symptoms.

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Acknowledgements

Kazuhide Higuchi and Toshihisa Takeuchi contributed to the concept and design of the study. We are grateful to the GERD-4 Study Group (Tetsuo Arakawa, Kazuma Fujimoto, Motoyasu Kusano, Kazunari Tominaga) for providing a useful reference for the design of this study. All authors approved the final version of the manuscript. We thank Nouvelle Place Inc. Tokyo, Japan, for their great support on data management and statistical analysis. We would like to thank Editage (www.editage.jp) for English language editing. We thank Chinatsu Saito, Yoshinori Ozaki of Tsumura Co., Ltd. Tokyo, Japan, who received information on hangeshashinto for research planning. This research was funded by Tsumura Co., Ltd. Tokyo, Japan.

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Authors and Affiliations

  1. Osaka Medical College Hospital Endoscopy Center, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan

    Toshihisa Takeuchi & Yuichi Kojima

  2. Fujita Gastroenterology Hospital, Osaka, Japan

    Hitoshi Hongo & Tsuguhiro Kimura

  3. Department of Internal Medicine II, Osaka Medical College Hospital, Osaka, Japan

    Satoshi Harada, Kazuhiro Ota & Kazuhide Higuchi

  4. Settsu Clinic, Osaka, Japan

    Nozomi Takeuchi

  5. Noguchi Clinic, Osaka, Japan

    Takao Noguchi

  6. Inoue Gastroenterology Clinic, Osaka, Japan

    Takuya Inoue

  7. Murano Clinic, Osaka, Japan

    Mitsuyuki Murano

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  1. Toshihisa Takeuchi
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Correspondence to Toshihisa Takeuchi.

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Kazuhide Higuchi has received honoraria from Tsumura Co,. Ltd.

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Takeuchi, T., Hongo, H., Kimura, T. et al. Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors. J Gastroenterol 54, 972–983 (2019). https://doi.org/10.1007/s00535-019-01588-4

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  • DOI: https://doi.org/10.1007/s00535-019-01588-4

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