Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study

Abstract

BackgroundProton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects.MethodsThirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment.ResultsThere was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031).ConclusionIrsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole.Trial registrationThis study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114)

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening

“…PPIs reduce the occurrence of peptic ulcers and are an important treatment for acute non-variceal upper gastrointestinal bleeding [21]. By contrast, acid inhibition does not confer protection to NSAID-induced damage distal to the ligament of Treitz [16,[22][23][24], and, in fact, studies report that PPIs could contribute to small intestinal injury. Wallace et al [13] and Blacker et al [25] have reported that PPIs exacerbate NSAID-induced small intestinal injury in rodents.…”

Mucosal Protective Agents Prevent Exacerbation of NSAID-Induced Small Intestinal Lesions Caused by Antisecretory Drugs in Rats

“…In addition to these promising developments, in the present study, we found that both IRS and REB as well as MIS could prevent the intestinal lesions caused by DIC with or without antisecretory drugs. Furthermore, several recent pilot studies using CE have revealed that both IRS (Kuramoto et al, 2013) and REB (Niwa et al, 2008;Mizukami et al, 2012), as well as MIS (Watanabe et al, 2008;Fujimori et al, 2009) are effective in limiting the small intestinal side effects of aspirin and other NSAIDs, including DIC. Taking all the present findings and the clinical findings in healthy volunteers together, it is concluded that both IRS and REB could be used as new candidate drugs for the treatment of intestinal lesions induced by NSAIDs with and without antisecretory drugs.…”

Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation

“…In recent studies, several drugs such as misoprostol [4], rebamipide [21-23], irsogladine [24], and probiotic Lactobacillus casei [25] have been reported to be effective for the treatment of NSAID-induced enteropathy, including enteropathy induced by LDA. However, these studies were limited by the characteristics of the subjects enrolled.…”