A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation

Abstract

Background: It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use. Aims: To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures. Patients: Women (>18 years of age) with IBS-C according to the Rome II criteria. Methods: Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat. Results: 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/ pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p,0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p,0.05). Conclusion: Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.

Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol – a randomized, double‐blind, placebo‐controlled study

“…Moreover, previous trials carried out with drugs having a clear-cut receptor-mediated effect have shown that even with such drugs, the therapeutic effect can be delayed: for instance, the statistical significant difference in improvement in abdominal discomfort ⁄ pain between 5-HT4 receptor agonist tegaserod and placebo was not reached before day 3 in a large sample of 2660 patients. 28 Another explanation for the progressive effect of P ⁄ TMP on visceral pain is a possible inhibitory effect on enzymes involved in the pathogenesis of pain, rather than a receptor-mediated effect. Based on the glycerol-induced visceral pain, animal studies suggested that P ⁄ TMP may modulate the release of prostaglandins and ⁄ or other inflammatory mediators such as nitric oxide.…”

Post-infectious irritable bowel syndrome

“…While the therapeutic gain associated with 5-HT3 antagonists [54][55][56][57][58][59][60][61][62] and 5-HT4 agonists [63][64][65][66][67][68][69][70][71][72] in treatment of sporadic IBS has been small, patients with PI-IBS are relatively more homogeneous and might demonstrate enhanced efficacy.…”

Bloating and functional gastro-intestinal disorders: Where are we and where are we going?

“…A combination of simethicone plus activated charcoal and magnesium oxide was tested against placebo in a double blind, ran- [136] Ⅱ Lactobacillus plantarum 299v: improvement [137] Ⅲ Multispecies: improvement [138] Ⅲ Symbiotics Symbiotic mixture: no benefits [115,116] Ⅲ Antibiotics Rifaximin: reduction in bloating-specific scores [110] Ⅱ Rifaximin: improvement (39.5% vs 28.7%) [112] Ⅱ Prokinetics Tegaserod: improvement [120] Ⅰ Tegaserod: improvement [139][140][141] Ⅱ Tegaserod: no differences vs placebo [142] Ⅱ Prucalopride: improvement [126] Ⅱ Antispasmodic Otilonium bromide improvement [143] Ⅱ Mebeverine vs Otilonium bromide: improvement significantly achieved by both treatments [144] Ⅱ Antidepressant Paroxetine: no difference vs placebo [145] Ⅰ Citalopram: improvement [146] Ⅱ Fluoxetine: improvement [147] Ⅱ domized, multicenter trial in patients with FD meeting the Rome Ⅲ criteria [134] . This study showed a reductions in the intensity of post-prandial fullness, epigastric pain, epigastric burning and bloating in the active treatment arm compared to placebo [134] .…”