Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives.
OBJECTIVE
To determine the efficacy, impact on quality of life (QOL) and safety of prucalopride, a selective, high-affinity 5-HT(4) receptor agonist, in patients with chronic constipation.


METHODS
In this multicentre, randomised, placebo controlled, parallel-group, phase III study, patients with chronic constipation (two or fewer spontaneous complete bowel movements (SCBM)/week) received 2 mg or 4 mg prucalopride or placebo, once daily, for 12 weeks. The primary efficacy endpoint was the proportion of patients reaching three or more SCBM/week. The key secondary efficacy endpoint was the proportion of patients having an increase of one or more SCBM/week. The primary QOL endpoint was the patient assessment of constipation QOL satisfaction subscale score. Safety parameters included adverse events, laboratory values and cardiovascular events.


RESULTS
Efficacy was evaluated over 713 patients. Averaged over 12 weeks, higher proportions of patients on prucalopride 2 mg (19.5%; p<0.01), 4 mg (23.6%; p<0.001) had three or more SCBM/week (or normalisation of bowel function) compared with placebo (9.6%). Similar results were seen in the subgroup (83%) of patients dissatisfied with previous laxative treatment. Both doses of prucalopride also significantly improved secondary efficacy and QOL endpoints, including the proportion of patients with an increase of one or more SCBM/week, evacuation completeness, perceived disease severity and treatment effectiveness and QOL. Prucalopride 4 mg significantly reduced the need for straining versus placebo (p<0.05). The most frequent treatment-related adverse events were headache and diarrhoea. Both doses of prucalopride were safe and well tolerated.


CONCLUSIONS
Prucalopride significantly and consistently improved bowel function, associated symptoms and satisfaction in chronically constipated patients.
Tack
J
J
Division of Gastroenterology, Department of Internal Medicine, University Hospital, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. Jan.Tack@med.kuleuven.be
van Outryve
M
M
Beyens
G
G
Kerstens
R
R
Vandeplassche
L
L
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001572:Benzofurans / Q000008:administration & dosage*; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy* / Q000523:psychology; D003672:Defecation / Q000187:drug effects*; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D054368:Laxatives / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D011788:Quality of Life / Q000523:psychology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D001572:Benzofurans; D054368:Laxatives; D017366:Serotonin Receptor Agonists; C406662:prucalopride