Lack of efficacy of ridogrel, a thromboxane synthase inhibitor, in a placebo-controlled, double-blind, multi-centre clinical trial in active Crohn's disease.
BACKGROUND
Thromboxanes are produced in excess and platelets are activated in active Crohn's disease. Preliminary reports have suggested that ridogrel, a dual thromboxane synthase inhibitor and receptor antagonist, may have therapeutic benefit in patients with inflammatory bowel disease.


OBJECTIVE
To investigate the efficacy of ridogrel in patients with active Crohn's disease.


METHODS
This was an international, multicentre, randomized, double-blind, placebo-controlled trial of 5 mg/day oral ridogrel for 12 weeks in 85 patients with moderately active Crohn's disease. Sixty patients were randomized to receive ridogrel, and 25 to placebo. The Crohn's disease activity index (CDAI) was used to assess disease activity: remission was defined as a CDAI < 150. Changes in clinical condition, as assessed by the Harvey-Bradshaw index, global evaluation by the investigator and the patient, and blood measures of inflammation, were used as secondary outcomes.


RESULTS
The patients' mean (s.d.) CDAI at recruitment was 277 (68) in the ridogrel treated group and 265 (70) in the placebo group. At their final assessment, 20 out of 60 (35%) patients who had been given ridogrel in an intention-to-treat analysis and seven out of 25 (28%) patients given placebo were in remission (no significant difference). No significant differences in Harvey- Bradshaw index or global evaluation were noted between patients given ridogrel and those given placebo. Adverse events were similar in both groups.


CONCLUSIONS
A 5-mg dose of oral ridogrel was not more effective than placebo in inducing remission in patients with moderately active Crohn's disease. If thromboxane synthesis and platelet function are to be targeted for the treatment of Crohn's disease, more potent agents require development and assessment.
Carty
E
E
Department of Adult and Paediatric Gastroenterology, St Bartholomew's and The Royal London School of Medicine, London, UK.
Rampton
D S
DS
Schneider
H
H
Rutgeerts
P
P
Wright
J P
JP
D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010352:Patient Dropouts; D010421:Pentanoic Acids / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D017211:Treatment Failure
D010421:Pentanoic Acids; D011725:Pyridines; D013930:Thromboxane-A Synthase; C060219:ridogrel