Saccharomyces boulardii Combined With Quadruple Therapy for Helicobacter pylori Eradication Decreased the Duration and Severity of Diarrhea: A Multi-Center Prospective Randomized Controlled Trial

Abstract

<b>Background:</b> Whether probiotics helped the <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication was still highly controversial. The non-bacterial <i>Saccharomyces boulardii</i> (<i>S. boulardii</i>) has demonstrated its efficacy in the treatment of antibiotic-associated and infectious diarrhea. We aimed to evaluate the effects of <i>S. boulardii</i> combined with quadruple therapy for <i>H. pylori</i> eradication and associated side effects. <b>Methods:</b> Three hundred and sixty <i>H. pylori-</i>infected patients were recruited in this multicenter, randomized controlled trial. The patients who underwent <i>H. pylori</i> eradication treatment were randomized in a ratio of 1:1 into two separate groups that received standard quadruple therapy (Group A) and quadruple therapy plus <i>S. boulardii</i> sachets (Group B) for 14 days. The everyday medication and side-effect records were collected for compliance and adverse effect analysis. All patients accepted ¹³C/¹⁴C-urea breath tests 4 weeks after the therapy completion. <b>Results:</b> <i>Saccharomyces boulardii</i> and quadruple therapy-combined intervention significantly reduced the incidences of overall side effects (27.8 vs. 38.5%, <i>p</i> = 0.034) and diarrhea (11.2 vs. 21.2%, <i>p</i> = 0.012) in Group B compared with quadruple therapy alone in Group A, especially reduced the diarrhea duration (5.0 days vs. 7.7 days, <i>p</i> = 0.032) and incidence of severe diarrhea (4.7 vs. 10.1%, <i>p</i> = 0.040). Intention-to-treat (ITT) analysis and per-protocol (PP) analysis both indicated no statistical differences of eradication rate between Groups A and B (ITT: 82.7 vs. 85.8%, <i>p</i> = 0.426; PP: 89.7 vs. 94.2%, <i>p</i> = 0.146). The joint use of <i>S. boulardii</i> and quadruple therapy markedly improved the overall pre-eradication alimentary symptoms (hazard ratio (HR): 2.507, 95% CI: 1.449-4.338) recovery. <b>Conclusion:</b> <i>Saccharomyces boulardii</i> ameliorated <i>H. pylori</i> eradication<i>-</i>induced antibiotic-associated side effects especially reduced the incidence of severe diarrhea and the duration of diarrhea. However, there was no significant effect of <i>S. boulardii</i> on the rate of <i>H. pylori</i> eradication. <b>Trial Registration:</b> The protocol had retrospectively registered at ClinicalTrails.gov, Unique identifier: NCT03688828, date of registration: September 27, 2018; https://clinicaltrials.gov/show/NCT03688828.