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
  Purpose

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 Intervention Phase
Pain, Postoperative
Drug: Ibuprofen + Paracetamol
Drug: Ibuprofen + Paracetamol + Codeine
Drug: Paracetamol + Codeine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Ullevaal University Hospital:

Primary Outcome Measures:
  • Sum pain intensity SPI (0-10 Numerical Rating Scale) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 200
Study Start Date: June 2009
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Placebo
  • Lactose
  • CAS No: 63-42-3

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.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00921700

Contacts
Contact: Lasse A Skoglund, DDS, DSci 004722844672 lasses@odont.uio.no
Contact: Per Skjelbred, DDS, MD, PhD 004722118484 p.skjelbred@ulleval.no

Locations
Norway
Ullevaal University Hospital Recruiting
Oslo, Norway, NO-0407
Contact: Lasse A Skoglund, DDS, DSci    004722844672    lasses@odont.uio.no   
Contact: Gaute Lyngstad, DDS    004722844673    gautelyn@odont.uio.no   
Principal Investigator: Gaute Lyngstad, DDS         
Sub-Investigator: Lasse A Skoglund, DDS, DSci         
Sponsors and Collaborators
Ullevaal University Hospital
University of Oslo
Investigators
Study Director: Lasse A Skoglund, DDS, DSci University of Oslo
Principal Investigator: Gaute Lyngstad, DDS University of Oslo
  More Information

Publications:
Responsible Party: Professor Lasse A. Skoglund, DDS, DSci, University of Oslo
ClinicalTrials.gov Identifier: NCT00921700     History of Changes
Other Study ID Numbers: PARIBU-022, EUDRACT No. 2007-001778-10
Study First Received: June 15, 2009
Last Updated: March 2, 2010
Health Authority: Norway:National Committee for Medical and Health Research Ethics
Norway: Norwegian Medicines Agency
Norway: Norwegian Social Science Data Services

Keywords provided by Ullevaal University Hospital:
Paracetamol
Acetaminophen
Ibuprofen
Pain
Postoperative pain
third molar

Additional relevant MeSH terms:
Analgesics
Analgesics, Non-Narcotic
Analgesics, Opioid
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Acetaminophen
Ibuprofen
Codeine
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014