Randomized Double-Blind Placebo-Controlled Trial of Rifaximin in Bloating and Flatulence

Abstract & Commentary

By Malcolm Robinson MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine, Oklahoma City. Dr. Robinson serves as a consultant for TAP, Pfizer, Janssen, Eisai, J&J-Merck, and Procter & Gamble, is on the speaker's bureau of Janssen, Eli Lilly, Solvay, TAP, and Aventis, and does research for Forest Labs, Wyeth-Ayerst, AstraZeneca, and Centocor.

Synopsis: Rifaximin appears to be safe and effective for treatment of abdominal bloating and flatulence in IBS.

Source: Sharara A, et al. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006;101:326-333.

All physicians recognize the ubiquity of irritable bowel syndrome (IBS) with its panoply of symptoms, uncertain etiology, and generally inadequate treatment options. Abdominal bloating has been reported in 15.9% of US adults, and flatulence is also an extremely common complaint. One hypothesized pathophysiology for some cases of IBS is small bowel bacterial overgrowth. However, even if this were a common etiology for IBS symptoms, treatment options have not been at all satisfactory. Rifaximin seems ideally suited for use in such a setting since this rifamycin derivative is active against aerobic and anaerobic bacteria and is not appreciably absorbed (thus being free of systemic side effects). Some preliminary studies of rifaximin suggest utility in treating small bowel bacterial overgrowth and reducing intestinal gas production.

This study at the American University in Beirut, Lebanon involved 124 patients with presumed gas-related symptoms of bloating and/or flatulence, none of whom had abnormal lactulose hydrogen breath tests at baseline (thus attempting to rule out conventional small bowel bacterial overgrowth as etiology for symptoms). Other variable symptoms of IBS were present at baseline in about one half of the patients. Symptoms had been present from 6 months to 7 years. No evidence of organic bowel disease was identified in these patients. Symptoms followed during the study were abdominal distention, pain, number of bowel movements, stool consistency, and sensation of incomplete stool evacuation. Rifaximin treatment for 10 days was associated with 41.3% of patients reporting decrease in symptom severity vs 22.9% of the placebo recipients. By 10 days post-treatment, relief was still present in 28.6% of rifaximin recipients vs 11.5% of those taking placebo. Patients with IBS by Rome II criteria may have had marginally better responses than those not meeting the Rome II IBS criteria. Even though breath hydrogen excretion was not abnormal at baseline, improvements seemed to correlate with decreases in hydrogen levels during the study. The authors speculate that changes in colonic microflora may be responsible for the beneficial effects of rifaximin in these patients.

Commentary

This is a laudable attempt by Professor Sharara and his colleagues to address a knotty clinical problem. It has been generally conceded by the gastroenterology community that no adequate treatments exist for the common complaints of bloating and flatulence. Most if not all of the varied and non-science based therapies used in this setting have placebo value at best (including prokinetic agents, various enzymes, charcoal, and simethicone). The authors comment that the study was relatively small, and they also admit that it had the potential disadvantage of combining patients with Rome II IBS with other patients who had isolated bloating and distention. They also strongly urged that further microbiologic studies be done to identify the particular strains of colonic flora most likely to be causative of IBS-related and other so-called functional lower GI symptomatology. They also warn that more data are needed regarding the best way to use an antibiotic like rifaximin, eg, continuous vs. intermittent therapy. Nevertheless, their findings have potential immediate relevance for clinicians who care for patients with some of these difficult syndromes.