Analgesic Effect of Ibuprofen, Paracetamol (Acetaminophen), and Paracetamol (Acetaminophen) Plus Codeine on Acute Pain

Ullevaal University Hospital

Status and phase: Completed; Phase 4

Conditions: Surgery

Treatments: Drug: Ibuprofen 400 mg; Drug: Paracetamol (acetaminophen) 500 mg; Drug: Ibuprofen 800 mg; Drug: Ibuprofen 600 mg; Drug: Paracetamol (acetaminophen) 1000 mg; Drug: Placebo; Drug: Paracetamol (acetaminophen) 1000 mg + codeine 60 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT00699114

PARIBU-020

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 estimated patients

Sex: All

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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350 participants in 7 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Single dose placebo capsule

Treatment:

Drug: Placebo

Ibuprofen 400 mg

Active Comparator group

Description:

Single dose ibuprofen 400 mg capsule

Treatment:

Drug: Ibuprofen 400 mg

Ibuprofen 600 mg

Active Comparator group

Description:

Single dose ibuprofen 600 mg capsule

Treatment:

Drug: Ibuprofen 600 mg

Ibuprofen 800 mg

Active Comparator group

Description:

Single dose ibuprofen 800 mg capsule

Treatment:

Drug: Ibuprofen 800 mg

Paracetamol 500 mg

Active Comparator group

Description:

Paracetamol 500 mg (acetaminophen) capsule

Treatment:

Drug: Paracetamol (acetaminophen) 500 mg

Paracetamol 1000 mg

Active Comparator group

Description:

Single dose paracetamol 1000 mg (acetaminophen) capsule

Treatment:

Drug: Paracetamol (acetaminophen) 1000 mg

Paracetamol 1000 mg + codeine 60 mg

Active Comparator group

Description:

Single dose paracetamol (acetaminophen) 1000 mg + codeine 60 mg capsule

Treatment:

Drug: Paracetamol (acetaminophen) 1000 mg + codeine 60 mg