Clinical trial NCT00699114: Analgesic Effect of Ibuprofen, Paracetamol (Acetaminophen), and Paracetamol (Acetaminophen) Plus Codeine on Acute Pain
Official title: Analgesic Effect of Ibuprofen 400, 600 and 800 mg, Paracetamol 500 and 1000 mg, and Paracetamol 1000 mg Plus 60 mg Codeine: Single-dose, Randomized, Placebo-controlled and Double-blind Study on Acute Pain After Third Molar Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Surgery
Keywords: Pain
Analgesics
Molar
Third
Acetaminophen
Paracetamol
Ibuprofen
Codeine
Placebo
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2008-06-17
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this placebo controlled clinical trial is to evaluate the dose response relationship of ibuprofen in doses from 400 mg to 800 mg and paracetamol (acetaminophen)in doses from 500 mg to 1000 mg compared with paracetamol (acetaminophen)1000 mg plus codeine 60 mg on acute postoperative pain after surgical removal of impacted third molars.

Detailed description: Acetaminophen (paracetamol) and related aspirin-like drugs have traditionally been used for pain control of minor to moderate postoperative pain. Gradually traditional non-steroidal anti-inflammatory drugs (NSAIDs) have become more popular as analgesics due to assumed superior therapeutic effects and aggressive marketing campaigns orchestrated by the pharmaceutical industry.

Ibuprofen is a widely used analgesic both in non-prescription and prescription doses.

A dose-response relationship for low ibuprofen doses is shown. Evidence of a progressing dose response relationship for moderate (i.e. 400 mg) to higher doses is scarce. A possible analgesic ceiling effect has been suggested for doses above 400 mg, although a correlation between given ibuprofen doses above 400 mg and patient serum levels is shown. However, it may be questioned if the plasma concentration of ibuprofen is an important determinator of analgesic drug efficacy. A higher dose is more likely to influence the duration of analgesic effect rather than the peak analgesic effect.

There are few clinical trials investigating the dose-response relationship of increasing ibuprofen doses and paracetamol doses. To our knowledge no published study has investigated the dose-response relationship of ibuprofen and paracetamol in the same trial with a negative (i.e. placebo) and a positive (i.e. best standard analgesic treatment) control group.

Eligibility criteria: Inclusion Criteria:

* Patients of both sexes referred for surgical removal of impacted third molars, due to symptoms or after being advised to do so by their dentist.
* Persons of both sexes (ASA type I).
* Females who are not pregnant or plan conception.
* Persons who have not used analgesics for 3 days prior to the day of surgery.
* Persons without known active ulcus or gastrointestinal bleeding.
* Persons without any known hypersensitivity for NSAIDs.
* Persons under no other continuous drug treatment than contraceptives.
* Caucasian origin.
* Persons with at least moderate postoperative pain as defined by subjective score on a verbal rating scale after surgical removal of third molars.

Exclusion Criteria:

* 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.
* Smoking before taking the test-drug or during the observation period.

Primary outcomes:
measure: Sum Pain Intensity Score(SPI)
timeFrame: 3 hour observation period
Secondary outcomes:
measure: Sum Pain Intensity Difference Score (SPID)
timeFrame: 3 hours
measure: Sum Pain Intensity Score (SPI)
timeFrame: 6 hours
measure: Sum Pain Intensity Difference Score (SPID)
timeFrame: 6 hours
measure: Maximum Pain Intensity Difference Score (MAXPID)
timeFrame: Unknown, calculated variable
measure: Time to Maximum Pain Intensity Difference Score
timeFrame: Unknown, calculated variable
measure: Self-reported Occurrence of Adverse Effects
timeFrame: 3 hours
measure: Self-reported Occurrence of Adverse Effects
timeFrame: 6 hours
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Department of Oral and Maxillofacial Surgery, Ullevaal University Hospital
Study officials:
affiliation: Section of Dental Pharmacology and Pharmacotherapy, ICD, Faculty of Dentistry, University of Oslo, POB 1119 Blindern, N-0317 Oslo, Norway
name: Lasse A Skoglund, DDS, DSCi
role: STUDY_CHAIR
affiliation: Department of Oral and Maxillofacial Surgery, Ullevaal University Hospital, Kirkeveien 166, N-0407 Oslo, Norway
name: Per Skjelbred, MD, DDS, PhD
role: STUDY_DIRECTOR
affiliation: Section of Dental Pharmacology and Pharmacotherapy, ICD, Faculty of Dentistry, University of Oslo, POB 1119 Blindern, N0317 Oslo, Norway
name: Gaute Lyngstad, DDS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lyngstad G, Skjelbred P, Swanson DM, Skoglund LA. Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study. Eur J Clin Pharmacol. 2021 Dec;77(12):1843-1852. doi: 10.1007/s00228-021-03231-9. Epub 2021 Oct 16.