TABLE 4.
Randomized controlled trials evaluating the efficacy of 5-HT3 receptor antagonists, rifaximin, and eluxadoline in IBS patients with diarrhea.
| Study | Population (n), Rome, women/men/mixed | Period (weeks) | Dose | Main outcome, significant difference compared to placebo | Adverse events |
|---|---|---|---|---|---|
| Alosetron (5-HT3 receptor antagonist) | |||||
| Krause et al. (2007), United States | IBS-D (n = 353, 177 alosetron), Rome II, women | 12 | 0.5 o.d. or 0.5 or 1 mg b.i.d | Improved global symptoms in all groups (RR: 51% 0.5 mg o.d., 48% 1 mg o.d., 43% 1 mg b.i.d., and 31% placebo) | Constipation |
| Chang et al. (2005), United States | IBS-D (n = 386, 258 alosetron), Rome I, men | 12 | 0.5 or 1 mg b.i.d | Adequate relief of global symptoms (RR: 53% vs. 40%) | Constipation ischemic colitis |
| Chey et al. (2004), United States | IBS-D (n = 569, 279 alosetron), Rome I, women | 48 | 1 mg b.i.d | Adequate relief of global symptoms (RR: 52% vs. 44%) | Constipation |
| Camilleri et al. (2001), United States | IBS-D (n = 626, 309 alosetron), Rome I, men | 12 | 1 mg b.i.d | Adequate relief of global symptoms (RR: 43% vs. 26%) | Constipation |
| Lembo et al. (2001), United States | IBS-D or IBS-M (n = 801, 532 alosetron), Rome II, women | 12 | 1 mg b.i.d | Improved global symptoms (RR: 76% vs 44%) | Constipation |
| Camilleri et al. (2000), United States | IBS-D or IBS-M (n = 647, 324 alosetron), Rome I, women | 12 | 1 mg b.i.d | Adequate relief of global symptoms (RR: 41% vs. 29%) | Constipation |
| Camilleri et al. (1999), United States | IBS-D or IBS-M (n = 152, 72 alosetron), Rome I, mixed | 12 | 1, 2, 4, 8 mg b.i.d | Adequate relief of global symptoms in women (RR: 60% 1 mg, 59% 2 mg, 51% 4 mg, 52% 8 mg, and 33% placebo) | Constipation |
| Ramosetron (5-HT 3 receptor antagonist) | |||||
| Fukudo et al. (2017), Japan | IBS-D (n = 305, 203 ramosetron), Rome III, women | 12 | 1.25, 2.5 or 5 μg o.d | Improved abdominal discomfort and pain (RR: 64% vs. 41%) | Constipation |
| Fukudo et al. (2016), Japan | IBS-D (n = 576, 292 ramosetron), Rome III, women | 12 | 2.5 μg o.d | Improved global symptoms (RR: 51% vs. 32%) | Constipation |
| Fukudo et al. (2014), Japan | IBS-D (n = 296, 147 ramosetron), Rome III, men | 12 | 5 μg o.d | Improved stool consistency (RR: 50% vs. 20%) | Hard stools |
| Matsueda et al. (2008a), Japan | IBS-D (n = 212, 103 ramosetron), Rome II, mixed | 12 | 5 or 10 μg o.d | Adequate relief of symptoms (5 μg 43%, 10 μg 43%, and placebo 27%) | Hard stools, constipation |
| Matsueda et al. (2008b), Japan | IBS-D (n = 539, 270 ramosetron), Rome II, mixed | 12 | 5 μg o.d | Adequate relief of symptoms (RR: 47% vs. 27%) | Hard stools, constipation |
| Ondansetron (5-HT 3 receptor antagonist) | |||||
| Plasse et al. (2020), United States | IBS-D (n = 126, 75 ondansetron), Rome III, mixed | 8 | 12 mg o.d. (bimodal release) | Improved stool consistency (RR: 56% vs. 35%) | Constipation, flatulence |
| Garsed et al. (2014), United Kingdom | IBS-D (n = 120), Rome III, mixed | 5 + 5 | 4 mg o.d | Cross-over study. Improved stool consistency, mean difference stool form (−0.9, 95% CI −1.1–-0.6) | Constipation |
| Rifaximin (Antibiotics) | |||||
| Pimentel et al. (2011), United States | IBS-D or IBS-M (n = 623, 309 rifaximin), Rome II, mixed | 2 | 550 mg t.i.d | Improved global symptoms (RR: 41% vs. 32%) | No differences with placebo |
| Pimentel et al. (2011), United States | IBS-D or IBS-M (n = 637, 316 rifaximin), Rome II, mixed | 2 | 550 mg t.i.d | Improved global symptoms (RR: 41% vs. 32%) | No differences with placebo |
| Lembo et al. (2016b), United States | IBS-D (n = 692 a , 328 rifaximin), Rome III, mixed (repeat treatment) | 2 | 550 mg t.i.d | More responders with improved global symptoms (RR: 38% vs. 32%) | Nausea |
| Eluxadoline (opioid receptors agonist) | |||||
| Brenner et al. (2019), Canada, United States | IBS- D (n = 346, 172 eluxadoline), Rome III, mixed | 12 | 100 mg b.i.d | Improved global symptoms (RR: 23% vs 10%) | Nausea, pain, constipation, vomiting |
| Lembo et al. (2016a), United States, Europe | IBS-D (n = 1,282, 855 eluxadoline), Rome III, mixed | 52 | 75 or 100 mg b.i.d | Improved stool consistency and abdominal pain, composite score (RR: 24% 75 mg, 25% 100 mg, and 17% placebo) | Nausea, pain, constipation, pancreatitis |
| Lembo et al. (2016a), United States, Europe | IBS-D (n = 1,146, 764 eluxadoline), Rome III, mixed | 26 | 75 or 100 mg b.i.d | Improved stool consistency and abdominal pain, composite score (RR: 29% 75 mg, 30% 100 mg, and 16% placebo) | Nausea, pain, constipation, pancreatitis |
| Dove et al. (2013), United States | IBS-D (n = 348, 176 eluxadoline), Rome III, mixed | 12 | 5, 25, 100, 200 mg b.i.d | Improved clinical response (RR: 12% 25 mg, 14% 200 mg, and 6% placebo) | Nausea, pain, constipation, pancreatitis |
a
Responders to rifaximin 550 mg t. i.d. 2 weeks with relapse of symptoms within 18 weeks, were randomized in repeat treatment or placebo.
5-HT, 5-hydroxytryptamin; b. i.d., twice daily; CI, confidence interval; GI, gastrointestinal; IBS, irritable bowel syndrome; IBS-D, IBS with predominant diarrhea; IBS-M, IBS with mixed bowel habits; o. d, once daily; RR, response rate; t. i.d., thrice daily.