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Previous Volume 358:2344-2354 May 29, 2008 Number 22 Next

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ABSTRACT

Background In this 12-week trial, we aimed to determine the efficacy of prucalopride, a selective, high-affinity 5-hydroxytryptamine₄ receptor agonist, in patients with severe chronic constipation.

Methods In our multicenter, randomized, placebo-controlled, parallel-group, phase 3 trial, patients with severe chronic constipation (2 spontaneous, complete bowel movements per week) received placebo or 2 or 4 mg of prucalopride, once daily, for 12 weeks. The primary efficacy end point was the proportion of patients having three or more spontaneous, complete bowel movements per week, averaged over 12 weeks. Secondary efficacy end points were derived from daily diaries and validated questionnaires completed by patients. Adverse events, clinical laboratory values, and cardiovascular effects were monitored.

Results Efficacy was analyzed in 620 patients. The proportion of patients with three or more spontaneous, complete bowel movements per week was 30.9% of those receiving 2 mg of prucalopride and 28.4% of those receiving 4 mg of prucalopride, as compared with 12.0% in the placebo group (P<0.001 for both comparisons). Over 12 weeks, 47.3% of patients receiving 2 mg of prucalopride and 46.6% of those receiving 4 mg of prucalopride had an increase in the number of spontaneous, complete bowel movements of one or more per week, on average, as compared with 25.8% in the placebo group (P<0.001 for both comparisons). All other secondary efficacy end points, including patients' satisfaction with their bowel function and treatment and their perception of the severity of their constipation symptoms, were significantly improved with the use of 2 or 4 mg of prucalopride as compared with placebo, at week 12. The most frequent treatment-related adverse events were headache and abdominal pain. There were no significant cardiovascular effects of treatment.

Conclusions Over 12 weeks, prucalopride significantly improved bowel function and reduced the severity of symptoms in patients with severe chronic constipation. Larger and longer trials are required to further assess the risks and benefits of the use of prucalopride for chronic constipation. (ClinicalTrials.gov number, NCT00483886 [ClinicalTrials.gov] .)

Source Information

From the College of Medicine, Mayo Clinic, Rochester, MN (M.C.); and Movetis, Turnhout, Belgium (R.K., A.R., L.V.).

Address reprint requests to Dr. Camilleri at the Mayo Clinic, Charlton 8-110, 200 First St. SW, Rochester, MN 55905, or at camilleri.michael{at}mayo.edu.

Full Text of this Article

This article has been cited by other articles:

• FOXX-ORENSTEIN, A. E., McNALLY, M. A., ODUNSI, S. T. (2008). Update on constipation: One treatment does not fit all. Cleveland Clinic Journal of Medicine 75: 813-823 [Abstract] [Full Text]  
• Fatima, A., LeLeiko, N. S. (2008). Treatment of Constipation - the Search Continues. AAP Grand Rounds 20: 41-42 [Full Text]  
• Moss, A. J. (2008). The Long and Short of a Constipation-Reducing Medication. NEJM 358: 2402-2403 [Full Text]