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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

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmacology, Université Victor Segalen, Hôpital Pellegrin, 33076, Bordeaux, France

    Nicholas Moore

  2. Clinical Pharmacology Department, University of Lyon, Lyon, France

    Eric Van Ganse

  3. Service de Rhumatologie, Hôpital Ambroise Paré, Boulogne-Billancourt, France

    Jean-Marie Le Parc

  4. Boots Healthcare International, Nottingham, England

    Richard Wall & Mahdi Farhan

  5. Boots Healthcare, Courbevoie, France

    Hélène Schneid, François Verrière & François Pelen

Authors
  1. Nicholas Moore
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  2. Eric Van Ganse
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  3. Jean-Marie Le Parc
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  4. Richard Wall
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  5. Hélène Schneid
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  6. Mahdi Farhan
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  7. François Verrière
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  8. François Pelen
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Correspondence to Nicholas Moore.

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Moore, N., Ganse, E.V., Parc, JM.L. et al. The PAIN Study: Paracetamol, Aspirin and Ibuprofen New Tolerability Study. Clin. Drug Investig. 18, 89–98 (1999). https://doi.org/10.2165/00044011-199918020-00001

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  • DOI: https://doi.org/10.2165/00044011-199918020-00001

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