title: Rifaximin Reduces the Number and Severity of Intestinal Lesions Associated With Use of Nonsteroidal Anti-Inflammatory Drugs in Humans.
abstract: The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36.
authors.affiliation: Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. Electronic address: scarpi@tin.it.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Scarpignato
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Dolak
authors.affiliation: Service of Digestive Diseases, Clinic Hospital Lozano Blesa, University of Zaragoza, Aragón Institute for Health Research (IIS Aragón), Centro de Investigatión Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Matzneller
authors.affiliation: Division of Clinical Research, Department of Research and Development, Alfa Wassermann SpA, Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Renzulli
authors.affiliation: Division of Clinical Research, Department of Research and Development, Alfa Wassermann SpA, Bologna, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Grimaldi
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: Department of Gastroenterology, King's College Hospital, London, United Kingdom.
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bjarnason
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D053704:Capsule Endoscopy; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology*; D007421:Intestine, Small / Q000382:microbiology / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D009853:Omeprazole / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin; D012720:Severity of Illness Index; D014456:Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D054328:Proton Pump Inhibitors; D012294:Rifamycins; D004008:Diclofenac; D009853:Omeprazole; D000078262:Rifaximin
keywords: Controlled Trial; Gastrointestinal Adverse Event; Microbiome; Prevention