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Prucalopride induces high‐amplitude propagating contractions in the colon of patients with chronic constipation: a randomized study
Author(s) -
Miner P. B.,
Camilleri M.,
Burton D.,
Achenbach H.,
Wan H.,
Dragone J.,
Mellgard B.
Publication year - 2016
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12832
Subject(s) - medicine , constipation , laxative , chronic constipation , adverse effect , prokinetic agent , clinical endpoint , gastroenterology , randomized controlled trial
Background This study compared prucalopride, a selective, prokinetic, 5‐ HT 4 receptor agonist, with polyethylene glycol 3350 + electrolytes ( PEG 3350), an osmotic laxative, on colonic motility parameters, primarily high‐amplitude propagating contractions ( HAPC s) in patients with chronic constipation. Methods This randomized, cross‐over, reader‐blinded study was conducted at a single site in the USA . The study was open to men and women aged 18–75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG 3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [ HAPC 1 ]) in the 12 h after treatment administration. Analyses were also conducted at two co‐primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm ( HAPC 2 ); and mean amplitude ≥75 mmHg, propagation ≥10 cm ( HAPC 3 ). Secondary endpoints included HAPC area under the curve ( AUC ), contraction force, amplitude, duration, and propagation velocity. Key Results Thirteen women were enrolled, with 12 completing the study. Significantly more HAPC 1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC 2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12‐h periods with prucalopride than with PEG 3350. Prucalopride significantly increased mean propagation distance and velocity ( HAPC 2 ) and mean AUC , force, and amplitude ( HAPC 3 ) compared with PEG 3350. Adverse events were mild or moderate. Conclusions & Inferences Prucalopride was superior to PEG 3350 in inducing HAPC s in patients with chronic constipation. ClinicalTrials.gov number NCT01707667.