Analgesic Effect of Paracetamol, Paracetamol + Codeine, Ibuprofen and Their Combination
Condition: Pain, Postoperative
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether the combination of paracetamol
      (acetaminophen) and other NSAIDs with or without weak opioids can give synergistic analgesic
      effect.
    

Detailed description: 
      Combining paracetamol and other NSAIDs could give a theoretical synergistic analgesic effect
      according to already known or assumed mechanisms of action. Synergism is defined as an
      additive or supra-additive effect not achieved by one of the drugs alone. Such synergism is
      shown in clinical studies between acetaminophen and naproxen in coxarthrosis and rheumatoid
      arthritis. Later, a significant additive effect of 100 mg diclofenac with 1 g acetaminophen
      was demonstrated in a dental pain model.

      One review article conclude that acetaminophen and NSAIDs may be appropriate to combine, and
      the combination is superior to acetaminophen, but not to NSAIDs alone. This view is contested
      by another review article which concludes that paracetamol may enhance the analgesic effect
      when added to an NSAID. In both reviews the authors also state that the clinical trials are
      too few, with different drug formulations, and different pain models not allowing definite
      conclusions.

      There seems to be a need for studies investigating the potential synergistic effects of
      paracetamol combined with another NSAID displaying similar pharmacokinetic characteristics.
      To the best of our knowledge no published study has investigated the analgesic effect of the
      combination of ibuprofen and paracetamol, ibuprofen and paracetamol + codeine versus placebo
      (i.e. negative control to adjust for possible analgesic placebo effects) and the best
      standard analgesic treatment (i.e. paracetamol + codeine) as a positive control group.
    

Intervention name(s): Ibuprofen + Paracetamol; Ibuprofen + Paracetamol + Codeine; Paracetamol + Codeine; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg in gelatine capsules; Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg and codeine 60 mg in gelatine capsules; Single oral dose of paracetamol (acetaminophen) 1000 mg combined with codeine 60 mg in gelatine capsules; Single oral dose of lactose as placebo in gelatine capsules
Other intervention name(s): Ibuprofen; ATC code: M01A E01; Paracetamol (Acetaminophen); ATC code: N02B E01; Ibuprofen; ATC code: M01A E01; Paracetamol (Acetaminophen); ATC code: N02B E01; Codeine; ATC code: R05D A04; Paracetamol (Acetaminophen); ATC code: N02B E01; Codeine; ATC code: R05D A04; Lactose; CAS No: 63-42-3
Intervention MeSH terms: Acetaminophen; Ibuprofen; Codeine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Paracetamol; Acetaminophen; Ibuprofen; Pain; Postoperative pain; third molar