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Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis.

ABSTRACT: Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813; and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at the start and end (4 or 12 weeks) of treatment. At these visits, patients assessed the presence and severity of their symptoms.In total, 280 patients had CTT measurements before and at the end of treatment and were included in the analysis. Their mean age was 43 years, 93% were women, and mean duration of constipation was 19 years. After a once daily treatment with prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95% confidence interval (CI): -18.9, -5.1) and 13.9 h (95% CI: -20.5, -7.4), respectively; CTT increased by 0.5 h (95% CI: -4.5, 5.5) with placebo (n=112). At the end of the trial, symptoms including bloating/flatulence/distension and straining were rated as severe or very severe by a higher proportion of patients with slow or very slow CTT (>48 h) than by those with normal CTT.There was a clear relationship between increased CTT and increased symptom severity in patients with chronic constipation. Treatment with prucalopride accelerated CTT in these individuals.

SUBMITTER: Emmanuel A

PROVIDER: S-EPMC4050523 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis.

Emmanuel Anton A Cools Marina M Vandeplassche Lieve L Kerstens René R

The American journal of gastroenterology 20140415 6

<h4>Objectives</h4>Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.<h4>Methods</h4>This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipa ...[more]

PMID: 24732867

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Project description:Aims:Radio-opaque markers have been widely used in the study of colon motility in patients with chronic functional constipation (FC). Here, we evaluate the relationship between the colon transit time (CTT) and the Boston Bowel Preparation Scale (BBPS) to determine whether CTT is a sufficient predictor of bowel preparation in patients with chronic functional constipation. Methods:A total of fifty-six patients with constipation and fifty-two healthy controls (HC) were enrolled in this study. All subjects underwent the colonic transit study using radio-opaque markers and were given a follow-up colonoscopy examination on day 3 to 7 to determine BBPS. The correlation between total and segmental CTT and BBPS was evaluated, and risk factors for predicting inadequate bowel preparation were determined. Results:In our study, we found some distinct outcomes compared with previous studies. The mean total CTT (TCTT) was determined to be 43.37 ± 18.82 h in the FC group and 23.08 ± 10.18 h in the HC group. This difference was found to be significant for both the total and segmental CTTs between the two groups (P < 0.05). Further, TCTT was negatively correlated with BBPS both in the FC (r = -0.899, 95% CI -0.748 to -0.925, P < 0.001) and the HC (r = -0.978, 95% CI -0.854 to -1.003, P = 0.004) groups, as was segmental CTTs and segmental BBPS (P < 0.05). In the case of patients with slow transit constipation, multivariate logistic regression analysis indicated that prolonged TCTT (OR 0.722, 95% CI 0.589-0.885, P = 0.002) was independently associated with poor bowel preparation. The total and right to left CTTs were found to predict inadequate bowel preparation and exhibited the best sensitivity and specificity at 48.0?h, 15.5?h, 17.5?h, and 19.0?h, based on ROC curve analysis. Conclusions:The CTT test represents a valuable method for predicting the level of bowel preparation prior to a colonoscopy examination. That is, both total and segmental CTTs can be considered an objective predictor of bowel preparation prior to colonoscopy. The present study demonstrates some distinct results relative to previous studies, including STC subtype proportion in FC, the proportion of inadequate bowel preparation in the STC subtype, and the cut-off value of TCTT for predicting inadequate bowel preparation.

Project description:Prucalopride is a selective, high-affinity, 5-hydroxytryptamine (serotonin) type 4 (5-HT4) receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three double-blind phase III trials (ClinicalTrials.gov: NCT00488137, NCT00483886, NCT00485940) compared the efficacy and safety of prucalopride 2?mg once daily in women with chronic constipation [?2 spontaneous complete bowel movements (SCBM) per week] in whom laxatives had failed to provide adequate relief with that in the all-patient (AP) population of men and women with chronic constipation who had or had not obtained relief from laxatives.Patients received prucalopride 2?mg or placebo once-daily for 12 weeks. Efficacy endpoints included an average of ?3 SCBM/week and average increases of ?1 SCBM/week and ?1 SBM/week over this period. A response on any of these three endpoints was considered to be clinically relevant, and an overall response rate was derived for patients satisfying any of these endpoints.Of the AP population (n?=?1318), 936 were women in whom laxatives had failed to provide adequate relief (WLF). More patients on prucalopride 2?mg than placebo had an average of ?3 SCBM/week (AP 24.4 vs 11.0%; WLF 24.7 vs 9.2%), an average increase of ?1 SCBM/week (AP 43.5 vs 24.8%; WLF 44.2 vs 22.6%), and an average increase of ?1 SBM/week (AP 66.7 vs 38.4%; WLF 68.3 vs 37.0%) (all p?<?0.001). Significant differences from placebo were evident in week 1 and sustained thereafter. Overall response rates in the AP and WLF populations, respectively, were 69.7 and 71.0% with prucalopride 2?mg and 44.5 and 41.6% with placebo (p?<?0.001). Early (weeks 1-4) response predicted ultimate response over time. Common (>10%) adverse events were abdominal pain, nausea, diarrhoea, and headache.Prucalopride 2?mg once daily is effective in WLF. The efficacy and safety profile observed in WLF was similar to that in the total evaluated population of patients with chronic constipation who had or had not obtained adequate relief from laxatives.

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Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis.

Publications

Prucalopride improves bowel function and colonic transit time in patients with chronic constipation: an integrated analysis.

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