Efficacy and safety of oral ridogrel in the treatment of ulcerative colitis: two multicentre, randomized, double-blind studies.
BACKGROUND
Ridogrel at low doses inhibits thromboxane synthase. Oral ridogrel, from 5 mg once daily to 150 mg twice daily, improves the endoscopic appearance of colonic mucosa and clinical manifestations in mild to moderate ulcerative colitis.


OBJECTIVE
One US trial and one international trial were conducted to determine the effect of ridogrel on mild to severe active ulcerative colitis.


METHODS
Two 12-week, double-blind, randomized, parallel-group trials were conducted. A US trial compared 0.5 mg, 2.5 mg and 5 mg of ridogrel once daily with placebo. An international trial compared 0.5 mg of ridogrel once daily with 2.5 mg and 5.0 mg of ridogrel once daily and 800 mg of mesalazine (known as mesalamine in the USA) three times daily. The primary efficacy outcome measure was the rate of complete remission.


RESULTS
In the US trial, complete remission was achieved in 20.8% of patients in the 0.5 mg ridogrel group, 17.9% in the 2.5 mg ridogrel group, 20.6% in the 5.0 mg ridogrel group and 13.6% in the placebo group. In the international trial, 14.4% of patients in the 0.5 mg ridogrel group, 19.6% in the 2.5 mg ridogrel group, 19.4% in the 5.0 mg ridogrel group and 16.4% in the mesalazine group experienced complete remission. In the international trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the 0.5 mg ridogrel group, but the differences were not statistically significant. In the US trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the placebo group, but the differences were not statistically significant. Approximately 30% of the patients in each group discontinued treatment before the 12-week end-point owing to a lack of therapeutic response. All doses of ridogrel were well tolerated and comparable with placebo or mesalazine in terms of safety.


CONCLUSIONS
No significant differences in the primary efficacy outcome measure were found between either the 2.5 mg or the 5.0 mg dose of ridogrel and placebo in the US trial and between either the 2.5 mg or the 5.0 mg dose of ridogrel and the 0.5 mg dose of ridogrel, a surrogate dose for placebo, in the international trial. There was no clear indication in either trial of an effective dose of ridogrel in the treatment of ulcerative colitis.
Tytgat
G N J
GN
Academisch Medisch Centrum, Amsterdam Zuidoost, The Netherlands. g.n.tytgat@amc.uva.nl
Van Nueten
L
L
Van De Velde
I
I
Joslyn
A
A
Hanauer
S B
SB
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000009:adverse effects / Q000494:pharmacology; D008875:Middle Aged; D010421:Pentanoic Acids / Q000009:adverse effects* / Q000494:pharmacology*; D010919:Placebos; D011725:Pyridines / Q000009:adverse effects* / Q000494:pharmacology*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005765:Gastrointestinal Agents; D010421:Pentanoic Acids; D010919:Placebos; D011725:Pyridines; D019804:Mesalamine; C060219:ridogrel