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A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury

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An Erratum to this article was published on 21 August 2013

Abstract

Background

It is not clear what kind of drug is appropriate to heal NSAID-induced enteropathy. Several reports showed the preventive effect of prostaglandin analogue or inducer using healthy subjects who took NSAIDs. However there was no report for healing effect and for patients. The aim of this study was to evaluate the healing effect of rebamipide in patients with NSAIDs-induced enteropathy. In addition, we evaluated for nutritional parameter.

Methods

This study was conducted as a randomized, double-blinded, placebo-controlled, multicenter trial. Study protocol was approved by each hospital’s ethical committees. Patients with LDA and/or NSAID more than 3 months were enrolled. Patients with enteropathy were divided into the placebo and the rebamipide groups. Rebamipide 100 mg three times daily was administered during 4 weeks. Capsule endoscopies were performed at 0 and 4 week. The number of small intestinal ulcer and erosion were evaluated. Total protein was analyzed as nutritional parameter.

Results

Sixty one participants were completed this study. Change in number of small intestinal erosion in the rebamipide group was −2.5 ± 3.4, and 2.1 ± 3.9 in the placebo group (P < 0.0001). Change in number of small intestinal ulcer in the rebamipide group was −0.5 ± 1.6, and 0.1 ± 0.7 in the placebo group (P = 0.024). Change in serum total protein levels in the rebamipide group was 0.06 ± 0.36, and −0.27 ± 0.34 in the placebo group (P = 0.0005).

Conclusions

Rebamipide has not only the healing effect for NSAIDs-induced enteropathy compared with placebo, but the improvement of nutritional condition. These results showed a tentative therapeutical strategy for chronic NSAIDs users.

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References

  1. Iddan G, Meron G, Glukhovsky A, Swain P. Wireless capsule endoscopy. Nature. 2000;405:417.

    Article  CAS  PubMed  Google Scholar 

  2. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3:55–9.

    Article  PubMed  Google Scholar 

  3. Lanas A, Garcia-Rodriguez LA, Polo-Tomas M, Ponce M, Alonso-Abreu I, Perez-Aisa MA, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol. 2009;104:1633–41.

    Article  PubMed  Google Scholar 

  4. Fujimori S, Seo T, Gudis K, Ehara A, Kobayashi T, Mitsui K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy. Gastrointest Endosc. 2009;69:1339–46.

    Article  PubMed  Google Scholar 

  5. Niwa Y, Nakamura M, Ohmiya N, Maeda O, Ando T, Itoh A, et al. Efficacy of rebamipide for diclofenac-induced small-intestinal mucosal injuries in healthy subjects: a prospective, randomized, double-blinded, placebo-controlled, cross-over study. J Gastroenterol. 2008;43:270–6.

    Article  CAS  PubMed  Google Scholar 

  6. Watanabe T, Sugimori S, Kameda N, Machida H, Okazaki H, Tanigawa T, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol. 2008;6:1279–82.

    Article  PubMed  Google Scholar 

  7. Fujimori S, Takahashi Y, Gudis K, Seo T, Ehara A, Kobayashi T, et al. Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury: a double-blind, randomized, controlled trial evaluated by capsule endoscopy. J Gastroenterol. 2011;46:57–64.

    Article  CAS  PubMed  Google Scholar 

  8. Mizukami K, Murakami K, Abe T, Inoue K, Uchida M, Okimoto T, et al. Aspirin-induced small bowel injuries and the preventive effect of rebamipide. World J Gastroenterol. 2011;17:5117–22.

    Article  CAS  PubMed  Google Scholar 

  9. Nishida U, Kato M, Nishida M, et al. Evaluation of gastrointestinal injury and blood flow of small bowel during low dose aspirin administration. J Clin Biochem Nutr. 2011;48:245–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Somasundaram S, Hayllar H, Rafi S, Wrigglesworth JM, Macpherson AJ, Bjarnason I. The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis. Scand J Gastroenterol. 1995;30:289–99.

    Article  CAS  PubMed  Google Scholar 

  11. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients: Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989;321:501–7.

    Article  CAS  PubMed  Google Scholar 

  12. Sostres C, Lanas A. Should prophylactic low-dose aspirin therapy be continued in peptic ulcer bleeding? Drugs. 2011;71:1–10.

    Article  CAS  PubMed  Google Scholar 

  13. The Esprit Study Group, Algra A. Medium intensity oral anticoagulants vs. aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomized controlled trial. Lancet Neurol. 2007;6:115–24.

    Google Scholar 

  14. Lanas A, Garcıa-Rodriguez LA, Arroyo MT, Bujanda L, Gomollon F, Forne M, et al. Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol. 2007;102:507–15.

    Article  CAS  PubMed  Google Scholar 

  15. Suzuki T, Yoshida N, Nakabe N, Isozaki Y, Kajikawa H, Takagi T, et al. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution. J Pharmacol Sci. 2008;106:469–77.

    Article  CAS  PubMed  Google Scholar 

  16. Kleine A, Kluge S, Peskar B. Stimulation of prostaglandin biosynthesis mediates gastroprotective effect of rebamipide in rats. Dig Dis Sci. 1993;38:1441–9.

    Article  CAS  PubMed  Google Scholar 

  17. Murata H, Yabe Y, Tsuji S, Tsujii M, Fu HY, Asahi K, et al. Gastro-protective agent rebamipide induces cyclooxygenase-2 in gastric epithelial cells. Dig Dis Sci. 2005;50:S70–5.

    Article  CAS  PubMed  Google Scholar 

  18. Hashimoto K, Oshima T, Tomita T, Kim Y, Matsumoto T, Joh T, et al. Oxidative stress induces gastric epithelial Permeability through claudin-3. Biochem Biophys Res Commun. 2008;376:154–7.

    Article  CAS  PubMed  Google Scholar 

  19. Mizoguchi H, Ogawa Y, Kanatsu K, Tanaka A, Kato S, Takeuchi K. Protective effect of rebamipide on indomethacin-induced intestinal damage in rats. J Gastroenterol Hepatol. 2001;16:1112–9.

    Article  CAS  PubMed  Google Scholar 

  20. Laharie D, Ménard S, Asencio C, Vidal-Martinez T, Rullier A, Zerbib F, et al. Effect of rebamipide on the colonic barrier in interleukin-10-deficient mice. Dig Dis Sci. 2007;52:84–92.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

Kato M disclosed the financial relationships about lecture fee and financial support from Eisai Co. Ltd., Takeda Pharmaceutical Co Ltd., AstraZeneca Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Astellas Pharma Co. Ltd., and Daiichi Sankyo Co. Ltd. The other authors declared that have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan

    Sei Kurokawa

  2. Center of Gastroenterology, Otaru Ekisaikai Hospital, Otaru, Japan

    Shinichi Katsuki & Tomoki Fujita

  3. Digestive Disease Center, Asahikawa City Hospital, Asahikawa, Japan

    Yusuke Saitoh

  4. Sapporo Orthopedic and Cardiovascular Hospital, Sapporo, Japan

    Hidetoshi Ohta

  5. Frano Kyoukai Hospital, Furano, Japan

    Kouji Nishikawa

  6. Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

    Yasushi Sato

  7. Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan

    Yasuhiro Sato

  8. Department of Gastroenterology, Iwamizawa Municipal General Hospital, Iwamizawa, Japan

    Koji Ohira

  9. Department of Gastroenterology, Shibetsu City Hospital, Shibetsu, Japan

    Masataka Yamada

  10. Division of Endoscopy, Hokkaido University Hospital, North 14, West 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan

    Mototsugu Kato

Authors
  1. Sei Kurokawa
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  2. Shinichi Katsuki
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  3. Tomoki Fujita
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  4. Yusuke Saitoh
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  5. Hidetoshi Ohta
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  6. Kouji Nishikawa
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  7. Yasushi Sato
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  8. Yasuhiro Sato
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  9. Koji Ohira
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  10. Masataka Yamada
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  11. Mototsugu Kato
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Correspondence to Mototsugu Kato.

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Kurokawa, S., Katsuki, S., Fujita, T. et al. A randomized, double-blinded, placebo-controlled, multicenter trial, healing effect of rebamipide in patients with low-dose aspirin and/or non-steroidal anti-inflammatory drug induced small bowel injury. J Gastroenterol 49, 239–244 (2014). https://doi.org/10.1007/s00535-013-0805-2

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  • DOI: https://doi.org/10.1007/s00535-013-0805-2

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