We designed a clinical trial to obtain dose-ranging, efficacy, and
aspirin-withdrawal data on
tiopinac in patients with
rheumatoid arthritis. To accomplish this without exposing the patients to risk of
disease exacerbation and avoiding type II error, we used a 3-phase protocol adding
tiopinac to current
therapy. The 3 phases-open-label dose ranging, double-blind
tiopinac versus placebo, and
aspirin withdrawal-began after a single-blind run-in period. The manufacturer withdrew
tiopinac from investigation because of toxicity at higher doses, but with only 13 patients we found that
tiopinac (up to 300 mg/day) decreased walking time, painful joints, and morning stiffness and increased grip strength (p less than 0.05). Both the global evaluation by the investigators and patient ratings of their activity showed superiority of
tiopinac (
tiopinac: 5 better, 1 worse; placebo: 1 better, 6 worse; p = 0.028 by Fisher's exact test). Complete
aspirin withdrawal could be accomplished in only 3 patients, although in 10 of 13 the dose could be reduced 50% of baseline or less. The 3-phase protocol indicated effectiveness, a dose range, and partial
aspirin replacement with minimal patient risk.