Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomized, double-blind, pilot study

Kazuhiro Ota,Kazuhide Higuchi,Toshihisa Takeuchi,Noriaki Sugawara,Kazuki Kakimoto,Takanori Kuramoto,Yuichi Kojima,Sadaharu Nouda,Yuki Hirata,Satoshi Harada

doi:10.1186/s12876-018-0923-7

Kazuhiro Ota, Kazuhide Higuchi + Show 8 more

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https://doi.org/10.1186/s12876-018-0923-7

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Abstract

BackgroundWe aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers.MethodsHealthy volunteers were enrolled randomly into one of two groups with the following drug regimens for 2 weeks: group A, low-dose aspirin once per day and group B, low-dose aspirin and 4.0 g of ecabet sodium. Small bowel capsule endoscopy was performed before and 2 weeks after low-dose aspirin administration.ResultsA significant difference was found in the median number [range] of small intestinal lesions between baseline and two weeks after low-dose aspirin administration in group A (baseline: 1 [0–5], after: 5 [1–11]; p = 0.0059) but not in group B (baseline: 0.5 [0–9], after: 3 [0–23]; p = 0.0586). In group B, although the median number [range] of lesions in the first tertile of the small intestine did not increase two weeks after low-dose aspirin administration (baseline: 0 [0–4], after: 1.5 [0–8]; p = 0.2969), the number of lesions in the second and third tertiles of the small intestine increased significantly (baseline: 0 [0–5], after: 2 [0–15]; p = 0.0469).ConclusionsEcabet sodium had a preventive effect on low-dose aspirin-induced small intestinal mucosal injury in the upper part of the small intestine.Trial registrationISRCTN 99322160, 01/10/2018.

Highlights

We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers
We excluded persons with history of peptic ulcer or gastrointestinal bleeding, significant hepatic, renal, heart, or respiratory disease, history of gastrointestinal surgery other than appendectomy, use of oral histamine H2-receptor antagonists, gastrointestinal kinetic agents, or gastric mucoprotective drugs within 2 weeks prior to the study, use of oral non-steroidal anti-inflammatory drugs (NSAIDs), steroids, anticholinergic drugs, anticancer drugs, or antithrombotic drugs within 4 weeks prior to the study, alcohol or chemical dependency, history of gastrointestinal obstruction, refusal to consent to the surgery that would be required if the capsule endoscope was retained in the body, and determination by the investigator, at his/her discretion, that a subject was ineligible for participation in the study for any reason
Evaluation of small intestinal mucosal lesions We examined small intestinal lesions using a PillCamSB (Given Imaging, Ltd., Yoquneam, Israel), an Small bowel capsule endoscopy (SBCE) device designed for assessing the small intestine

Summary

Introduction

We aimed to investigate how high-dose ecabet sodium affects low-dose aspirin-induced small intestinal mucosal injury in healthy volunteers. Low-dose aspirin (LDA) exerts antiplatelet effects by inhibiting cyclooxygenase-1 activity and suppressing prostaglandin production; the reduction in prostaglandins causes whole intestinal mucosal injury [1,2,3]. It is recommended that LDA users concurrently use a proton pump inhibitor (PPI) to prevent LDA-induced upper gastrointestinal mucosal injury [4, 5]. It has been reported that several gastric mucoprotective drugs are effective for preventing LDA-induced small intestinal mucosal injury [5,6,7,8,9,10]. Rebamipide, a gastric mucoprotective drug, effectively prevents LDAinduced gastrointestinal mucosal injury by stimulating production of prostaglandin and epidermal growth factor [11]. We reported that rebamipide inhibited increases in fecal levels of calprotectin, an inflammatory biomarker of the lower intestinal mucosa for LDA [6, 12]

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