Clinical Drug Investigation

, Volume 18, Issue 2, pp 89–98 | Cite as

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
  • Nicholas Moore
  • Eric Van Ganse
  • Jean-Marie Le Parc
  • Richard Wall
  • Hélène Schneid
  • Mahdi Farhan
  • François Verrière
  • François Pelen
Clinical Use


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 daily), 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.


Aspirin Adis International Limited Ibuprofen Paracetamol Significant Adverse Event 
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Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Nicholas Moore
    • 1
  • Eric Van Ganse
    • 2
  • Jean-Marie Le Parc
    • 3
  • Richard Wall
    • 4
  • Hélène Schneid
    • 5
  • Mahdi Farhan
    • 4
  • François Verrière
    • 5
  • François Pelen
    • 5
  1. 1.Department of PharmacologyUniversité Victor Segalen, Hôpital PellegrinBordeauxFrance
  2. 2.Clinical Pharmacology DepartmentUniversity of LyonLyonFrance
  3. 3.Service de RhumatologieHôpital Ambroise ParéBoulogne-BillancourtFrance
  4. 4.Boots Healthcare InternationalNottinghamEngland
  5. 5.Boots HealthcareCourbevoieFrance

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