Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trial.
BACKGROUND
Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin(4) receptor agonist with enterokinetic properties.


OBJECTIVE
Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre.


METHODS
After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study).


RESULTS
Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters.


CONCLUSIONS
Once-daily prucalopride 4 mg for 4 weeks is effective and well tolerated in patients with severe CC. It improves whole gut transit, reducing straining, softening stools and reducing time to first bowel movement.
Department of Gastroenterology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium. georges.coremans@uz.kuleuven.ac.be
Georges
G
Coremans
René
R
Kerstens
Martine
M
De Pauw
Marita
M
Stevens
D000328:Adult; D001572:Benzofurans / Q000627:therapeutic use*; D002400:Cathartics / Q000627:therapeutic use*; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012449:Safety; D012702:Serotonin Antagonists / Q000627:therapeutic use; D012720:Severity of Illness Index
D001572:Benzofurans; D002400:Cathartics; D012702:Serotonin Antagonists; C406662:prucalopride