Background : Cyclooxygenase‐2 selective inhibitors were developed in order to reduce the incidence of life‐threatening gastrointestinal ulcer complications compared with non‐selective non‐steroidal anti‐inflammatory drugs. Previous outcomes studies have, variously, lacked power to investigate this endpoint, focused on broader outcomes, or been too small to quantify the influence of aspirin.

Aim : To evaluate lumiracoxib, a novel cyclooxygenase‐2 selective inhibitor, vs. non‐selective non‐steroidal anti‐inflammatory drugs in an outcomes study of considerably increased size. This paper describes the study's methodology.

Methods and patients : The Therapeutic Arthritis Research and Gastrointestinal Event Trial was a randomized, double‐blind, 52‐week study of lumiracoxib 400 mg once daily (two to four times the recommended dose for osteoarthritis) versus naproxen 500 mg twice daily or ibuprofen 800 mg three‐times daily in patients with osteoarthritis. Randomization was stratified for low‐dose aspirin use and age (≤ 64, 65–74, ≥ 75 years). The study was powered to investigate upper gastrointestinal ulcer complications (primary endpoint) in patients not taking aspirin and in the overall study population; other endpoints included cardiovascular, renal and hepatic measures.

Conclusions : Therapeutic Arthritis Research and Gastrointestinal Event Trial was designed to provide definitive answers concerning the gastrointestinal safety of lumiracoxib, addressing the controversial issues arising from outcomes studies with other cyclooxygenase‐2 selective inhibitors.