The PAIN study:: Paracetamol, aspirin and ibuprofen new tolerability study -: A large-scale, randomised clinical trial comparing the tolerability of aspirin, ibuprofen and paracetamol for short-term analgesia

Objective: This study aimed to compare directly aspirin (acetylsalicylic acid), ibuprofen and paracetamol (acetaminophen), first-line analgesics which are generally well tolerated. from a safety perspective in general practice. Methods: This was a blinded, multicentre study in general practice of up to 7 days of aspirin, paracetamol (both up to 3g daily) or ibuprofen (up to 1.2g dairy), administered for common painful conditions, using patient-generated data with physician assistance. The main outcome was the rate of significant adverse events (serious, severe or moderate events. events resulting in treatment discontinuation or a physician visit). Statistical analysis tested for equivalence between ibuprofen and paracetamol, and for difference with aspirin. Results: 1108 general practitioners included 8677 adults (2900 aspirin, 2886 ibuprofen, 2888 paracetamol; three patients had no code label number). 8633 (99.5%) were evaluable, of whom 8233 (95%) adhered to the study protocol. The main indications were musculoskeletal or back pain (48%), sore throat, the common cold and flu (31%). Rates of significant adverse events were: aspirin 18.7%, ibuprofen 13.7%, and paracetamol 14.5%. Ibuprofen was statistically equivalent to paracetamol. Both were significantly better tolerated than aspirin (p < 0.001). Total gastrointestinal events (including dyspepsia) and abdominal pain were less frequent with ibuprofen (4 and 2.8%, respectively) than with paracetamol (5.3 and 3.9%) or aspirin (7.1 and 6.8%) [all p < 0.035]. There were six cases of non-serious gastrointestinal bleeding, four with paracetamol and two with aspirin, and one case of peptic ulcer with aspirin. Conclusion: The overall tolerability of ibuprofen in this large-scale study was equivalent to that of paracetamol and better than that of aspirin. These findings could lead to a reassessment of the use of first-line analgesics for the short-term management of painful conditions in general practice, recommending ibuprofen first, because of the poor tolerability of aspirin and the potential risks of paracetamol overdose.