Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Analgesic Effect of Paracetamol, Paracetamol + Codeine, Ibuprofen and Their Combination

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Ullevaal University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Oslo
Information provided by:
Ullevaal University Hospital
ClinicalTrials.gov Identifier:
NCT00921700
First received: June 15, 2009
Last updated: March 2, 2010
Last verified: March 2010

June 15, 2009
March 2, 2010
June 2009
June 2011   (final data collection date for primary outcome measure)
Sum pain intensity SPI (0-10 Numerical Rating Scale) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00921700 on ClinicalTrials.gov Archive Site
  • Sum pain intensity difference score (PID) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Overall assessment of efficacy (4-point Verbal Rating Scale) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
  • Adverse effects AE (Specific reporting of AE - type, duration and severity) [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Analgesic Effect of Paracetamol, Paracetamol + Codeine, Ibuprofen and Their Combination
Analgesic Effect of Ibuprofen 400 mg/Paracetamol 1000 mg, Ibuprofen 400 mg/ Paracetamol 1000 mg/60 mg Codeine, and Paracetamol 1000 mg/Codeine 60 mg: A Single-dose, Randomized, Placebo-controlled and Double-blind Study

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pain, Postoperative
  • Drug: Ibuprofen + Paracetamol
    Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg in gelatine capsules
    Other Names:
    • Ibuprofen
    • ATC code: M01A E01
    • Paracetamol (Acetaminophen)
    • ATC code: N02B E01
  • Drug: Ibuprofen + Paracetamol + Codeine
    Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg and codeine 60 mg in gelatine capsules
    Other Names:
    • Ibuprofen
    • ATC code: M01A E01
    • Paracetamol (Acetaminophen)
    • ATC code: N02B E01
    • Codeine
    • ATC code: R05D A04
  • Drug: Paracetamol + Codeine
    Single oral dose of paracetamol (acetaminophen) 1000 mg combined with codeine 60 mg in gelatine capsules
    Other Names:
    • Paracetamol (Acetaminophen)
    • ATC code: N02B E01
    • Codeine
    • ATC code: R05D A04
  • Drug: Placebo
    Single oral dose of lactose as placebo in gelatine capsules
    Other Names:
    • Placebo
    • Lactose
    • CAS No: 63-42-3
  • Experimental: Ibuprofen + Paracetamol
    Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg
    Intervention: Drug: Ibuprofen + Paracetamol
  • Experimental: Ibuprofen + Paracetamol + Codeine
    Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg + codeine 60 mg
    Intervention: Drug: Ibuprofen + Paracetamol + Codeine
  • Active Comparator: Paracetamol + Codeine
    Single oral dose of paracetamol (acetaminophen) 1000 mg + codeine 60 mg
    Intervention: Drug: Paracetamol + Codeine
  • Placebo Comparator: Placebo
    Single oral dose of lactose as placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
June 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients of ASA class I in need of surgical removal of impacted third molars and with at least moderate postoperative pain as defined by subjective score on a verbal rating scale after surgical removal of third molars.

Exclusion Criteria:

  • Females stating not suspected or not verified pregnancy after being questioned by investigator.
  • Patients who have used analgesics for 3 days prior to the day of surgery.
  • Patients with known active gastrointestinal bleeding or ulcer.
  • Patients with any known hypersensitivity to NSAIDs.
  • Patients with other drug treatment than contraceptives.
  • Patients smoking before taking the test-drug or during the observation period.
  • Drug addicts or rehabilitated drug addicts.
  • Patients with surgery time exceeding 60 minutes
  • Peroperative complications such as profuse bleeding or perforation to the maxillary sinus requiring additional drug treatment during or after the surgical removal of the third molar.
  • Postoperative complications such as extended bleeding, nausea and regurgitation during the observation period.
Both
18 Years to 30 Years
No
Contact: Lasse A Skoglund, DDS, DSci 004722844672 lasses@odont.uio.no
Contact: Per Skjelbred, DDS, MD, PhD 004722118484 p.skjelbred@ulleval.no
Norway
 
NCT00921700
PARIBU-022, EUDRACT No. 2007-001778-10
No
Professor Lasse A. Skoglund, DDS, DSci, University of Oslo
Ullevaal University Hospital
University of Oslo
Study Director: Lasse A Skoglund, DDS, DSci University of Oslo
Principal Investigator: Gaute Lyngstad, DDS University of Oslo
Ullevaal University Hospital
March 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP