Characteristics of randomised controlled trials of pharmacological therapies versus placebo in IBS-D or IBS-M
| Study | Country and number of centres | Diagnostic criteria used for IBS and subtypes of IBS recruited | Primary endpoint used to define symptom improvement following therapy by the original investigators | Number of patients (% female) | Number of patients assigned to active drug, dosage, schedule and duration of therapy |
| Camilleri et al 35 | Multinational, 68 sites. | Rome I criteria, 100% IBS-D or IBS-M. | Adequate relief of pain and discomfort for ≥6 of the 12 weeks of therapy. | 152 (44.1). | 72 patients received alosetron 1 mg twice daily for 12 weeks. |
| Camilleri et al 18 | USA, 119 sites. | Rome I criteria, 70.8% IBS-D, 27.8% IBS-M. | Adequate relief of IBS pain and discomfort for ≥2 weeks per month for each of 3 months. | 647 (100). | 324 patients received alosetron 1 mg twice daily for 12 weeks. |
| Camilleri et al 34 | USA, 104 sites. | Rome I criteria, 71.2% IBS-D, 27.0% IBS-M. | Adequate relief of IBS pain and discomfort for ≥2 weeks per month for each of 3 months. | 626 (100). | 309 patients received alosetron 1 mg twice daily for 12 weeks. |
| Lembo et al 38 | USA, 180 sites. | Rome II criteria, 97.8% IBS-D, 2.2% IBS-M. | Substantial or moderate improvement in global IBS symptoms over the last 4 weeks of therapy. | 801 (100). | 532 patients received alosetron 1 mg twice daily for 12 weeks. |
| Chey et al 36 | Multinational, 138 sites. | Rome I criteria, 100% IBS-D.† | Weekly adequate relief of IBS pain and discomfort at week 48 of treatment.‡ | 569 (100). | 279 patients received alosetron 1 mg twice daily for 48 weeks. |
| Chang et al 37 | USA and Canada, 186 sites. | Rome I criteria, 100% IBS-D. | Adequate relief of IBS pain and discomfort for weeks 5–12 of treatment. | 386 (0). | 127 patients received alosetron 0.5 mg twice daily and 131 received alosetron 1 mg twice daily for 12 weeks. |
| Krause et al 39 | USA, number of sites not reported. | Rome II criteria, 100% IBS-D. | Moderate or substantial improvement in global IBS symptoms over the last 4 weeks of therapy. | 353 (100). | 177 patients received alosetron 1 mg twice daily for 12 weeks. |
| Matsueda et al 41 | Japan, number of sites not reported. | Rome II criteria, 100% IBS-D. | Complete or considerable relief of global IBS symptoms for ≥2 of the last 4 weeks of therapy. | 212 (27.3). | 103 patients received ramosetron 5 µg once daily for 12 weeks. |
| Matsueda et al NCT0018969640 | Japan, number of sites not reported. | Rome II criteria, 100% IBS-D. | Complete or considerable relief of global IBS symptoms for ≥2 of the last 4 weeks of therapy. | 539 (17.9). | 270 patients received ramosetron 5 µg once daily for 12 weeks. |
| Fukudo et al NCT0122523742 | Japan, 52 sites. | Rome III criteria, 100% IBS-D. | A weekly mean BSFS score of≥3 to ≤5 and a decrease of ≥1 point in mean BSFS score from baseline for ≥2 of the first 4 weeks of therapy.‡ | 296 (0). | 147 patients received ramosetron 5 µg once daily for 12 weeks. |
| Fukudo et al NCT0187089519 | Japan, 70 sites. | Rome III criteria, 100% IBS-D. | Complete or considerable relief of global IBS symptoms for ≥2 of the last 4 weeks of therapy. | 576 (100). | 292 patients received ramosetron 2.5 µg once daily for 12 weeks. |
| Fukudo et al NCT0127400043 | Japan, 61 sites. | Rome III criteria, 100% IBS-D. | Complete or considerable relief of global IBS symptoms for ≥2 of the last 4 weeks of therapy. | 305 (100). | 104 and 99 patients received ramosetron 2.5 µg or 5 µg once daily, respectively, for 12 weeks. |
| Pimentel et al
(Target 1) NCT0073167917 | USA and Canada, 179 sites. | Rome II criteria, 100% IBS-D or IBS-M. | Adequate relief of global IBS symptoms for ≥2 of the first 4 weeks after therapy.‡ | 623 (73.4). | 309 patients received rifaximin 550 mg three times daily for 2 weeks. |
| Pimentel et al
(Target 2) NCT0072412617 | USA and Canada, 179 sites. | Rome II criteria, 100% IBS-D or IBS-M. | Adequate relief of global IBS symptoms for ≥2 of the first 4 weeks after therapy.‡ | 637 (71.2). | 316 patients received rifaximin 550 mg threee times daily for 2 weeks. |
| Dove et al NCT0113027244 | USA, 263 sites. | Rome III criteria, 100% IBS-D. | ≥30% reduction in worst abdominal pain score and at least two points, and a daily BSFS score of 3 or 4 on ≥66% of daily diary entries at week 4.‡ | 348 (69.3). | 176 patients received eluxadoline 100 mg twice daily for 12 weeks. |
| Lembo et al
(IBS-3001) NCT0155359120 | USA, Canada and UK, 295 sites. | Rome III criteria, 100% IBS-D. | ≥30% reduction in worst abdominal pain score on ≥50% of days and, on the same days, a daily BSFS score of <5 at week 12. | 1282 (65.4). | 429 and 426 patients received eluxadoline 75 mg or 100 mg twice daily, respectively, for 26 weeks. |
| Lembo et al
(IBS-3002) NCT0155374720 | USA, Canada and UK, 261 sites. | Rome III criteria, 100% IBS-D. | ≥30% reduction in worst abdominal pain score on ≥50% of days and, on the same days, a daily BSFS score of <5 at week 12. | 1146 (67.0). | 381 and 383 patients received eluxadoline 75 mg or 100 mg twice daily, respectively, for 26 weeks. |
| Brenner (RELIEF) NCT0295998347 | USA and Canada, number of sites not reported. | Rome III criteria, 100% IBS-D. | ≥40% reduction in worst abdominal pain score on ≥50% of days and a daily BSFS score of <5 at week 12. | 346 (69.9). | 172 patients received eluxadoline 100 mg twice daily for 12 weeks. |
†Also recruited patients with IBS-M, but data were only extractable for those with IBS-D at 12 weeks.
‡Efficacy data were extracted at 12 weeks for the purpose of this analysis.
BSFS, Bristol Stool Form Scale; IBS-D, IBS with diarrhoea; IBS-M, IBS with mixed stool pattern.