Comparative evaluation of gastrointestinal intolerance produced by plain and tri-buffered aspirin tablets.

Two multi-investigator, double-blind, randomized, placebo-controlled, crossover trials were conducted to determine whether tri-buffered formulations of both regular strength aspirin and extra strength aspirin would be less likely than plain aspirin to provoke subjective gastrointestinal (GI) intolerance. Each trial was divided into two phases, a qualification phase and a test phase. During the qualification phase, subjects with a history of gastrointestinal intolerance to aspirin were randomized to a double-blind crossover treatment with aspirin and placebo (325 mg aspirin per tablet in study 1 and 500 mg aspirin per tablet in study 2), two tablets four times a day for 3 days or until the occurrence of stomach upset. Subjects who reported gastrointestinal symptoms with aspirin and not with placebo qualified to participate in the test phase of the study. They were rerandomized to participate in a three-way crossover study of plain aspirin, tri-buffered aspirin, and placebo in the test phase. Tri-buffered aspirin was associated with an appreciable reduction in the incidence of gastrointestinal upset relative to plain aspirin, 34 percentage points in study 1 (p less than 0.001) and 33 percentage points in study 2 (p less than 0.001). Similar results were obtained in the evaluation of the reduction of the severity of gastrointestinal symptoms.