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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00921700
Recruitment Status : Completed
First Posted : June 16, 2009
Last Update Posted : March 30, 2016
Sponsor:
Collaborator:
University of Oslo
Information provided by (Responsible Party):
Lasse Ansgar Skoglund, Oslo University Hospital

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Pain, Postoperative Drug: Ibuprofen + Paracetamol Drug: Ibuprofen + Paracetamol + Codeine Drug: Paracetamol + Codeine Drug: Placebo Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2009
Actual Primary Completion Date : November 2014
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Ibuprofen + Paracetamol
Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg
 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
Experimental: Ibuprofen + Paracetamol + Codeine
Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg + codeine 60 mg
 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
Active Comparator: Paracetamol + Codeine
Single oral dose of paracetamol (acetaminophen) 1000 mg + codeine 60 mg
 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
Placebo Comparator: Placebo
Single oral dose of lactose as placebo
 Drug: Placebo
Single oral dose of lactose as placebo in gelatine capsules
Other Names:
  • Lactose
  • CAS No: 63-42-3


Outcome Measures
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Primary Outcome Measures :
  1. Sum pain intensity SPI (0-10 Numerical Rating Scale) [ Time Frame: 6 hours ]

Secondary Outcome Measures :
  1. Sum pain intensity difference score (PID) [ Time Frame: 6 hours ]
  2. Overall assessment of efficacy (4-point Verbal Rating Scale) [ Time Frame: 6 hours ]
  3. Adverse effects AE (Specific reporting of AE - type, duration and severity) [ Time Frame: 6 hours ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00921700


Locations
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Norway
Ullevaal University Hospital
Oslo, Norway, NO-0407
Sponsors and Collaborators
Ullevaal University Hospital
University of Oslo
Investigators
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Study Director: Lasse A Skoglund, DDS, DSci University of Oslo
Principal Investigator: Gaute Lyngstad, DDS University of Oslo
More Information
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Publications:

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Responsible Party: Lasse Ansgar Skoglund, Professor, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT00921700    
Other Study ID Numbers: PARIBU-022
EUDRACT No. 2007-001778-10
First Posted: June 16, 2009    Key Record Dates
Last Update Posted: March 30, 2016
Last Verified: March 2016
Keywords provided by Lasse Ansgar Skoglund, Oslo University Hospital:
Paracetamol
Acetaminophen
Ibuprofen
 Pain
Postoperative pain
third molar
Additional relevant MeSH terms:
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Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Acetaminophen
Ibuprofen
Codeine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
 Antipyretics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents