Rifaximin for the treatment of functional dyspepsia: a double-blinded randomized placebo-controlled trial

Abstract

BACKGROUND: Patients with functional dyspepsia (FD) frequently present with bloating and belching. Rifaximin has been shown to be effective in treatment of non-constipated irritable bowel syndrome (IBS). Individual symptom analyses also showed that there was significant reduction of bloating symptoms with rifaximin. We performed a pilot double-blinded, randomized, placebo-controlled trial to evaluate the effects of rifaximin as a treatment for FD. METHODS: Patients who had FD as per the ROME III criteria were randomized to receive either rifaximin 400mg TDS or identical looking placebo TDS for two weeks. We excluded patients with predominant symptoms more suggestive of IBS. All patients had normal upper endoscopy and were negative for H. pylori on entry of study. Subjects were assessed at 2, 4 and 8 weeks for symptoms. The primary end point was the proportion of patients who had adequate relief of global dyspepsia symptoms (GDS) at week 4. Adequate relief was defined as self-reported GDS of 'nil to mild' symptoms as measured on a 4-point scale (nil, mild, moderate or severe). Other secondary end points included the proportion of patients who had adequate relief of GDS at week 8, and other FD-related symptoms (bloating, belching, abdominal pain, epigastric pain, flatulence, nausea and vomiting) at week 4. Analysis was based on intention-to-treat. RESULTS: A total of 81 patients were included in the study: 39 were randomised to rifaximin. 61 (75.3%) were female and the mean age was 53.5 (±12.8) years. The two groups were comparable in all baseline characteristics including GDS and other FD-related symptoms. At week 4, 33.3% of the rifaximin group and 58.8% of placebo groups still had 'moderate-to-severe' GDS, respectively (P=0.036; Figure 1). The relative risk (RR) for 'moderate-to-severe' GDS in the rifaximin group at week 4 was 0.60 (95% Confidence Interval (CI) 0.37-0.98). For bloating symptoms at week 4, 23.1% of the rifaximin group and 54.8% of the placebo group still experienced 'moderate-to-severe' symptoms (RR for rifaximin group = 0.44; 95% CI 0.21 to 0.93; P=0.02). There was also a trend favoring rifaximin for belching symptoms (19.2% vs. 42.4% in placebo group experiencing 'moderate-to-severe' symptoms; P=0.058). There was no significant difference between the two groups in other FD symptoms including pain, nausea and vomiting and flatulence. The rates of adverse events of the rifaximin and placebo groups were comparable (10.1% Vs. 17.7%, P=0.20). CONCLUSIONS: The results of this pilot study demonstrate that rifaximin is effective in the treatment of FD, particularly in the relief of GDS and bloating symptoms. A large scale randomized controlled trial should be considered.