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

Sponsor

Ullevaal University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00699114

Collaborator

University of Oslo (Other)

350

Enrollment

Location

Arms

Duration (Months)

11.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Surgery	Drug: Placebo Drug: Ibuprofen 400 mg Drug: Ibuprofen 600 mg Drug: Ibuprofen 800 mg Drug: Paracetamol (acetaminophen) 500 mg Drug: Paracetamol (acetaminophen) 1000 mg Drug: Paracetamol (acetaminophen) 1000 mg + codeine 60 mg	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

350 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, 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 Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Single dose placebo capsule	Drug: Placebo Lactose as powder in gelatine capsules, single dose Other Names: Lactose
Active Comparator: Ibuprofen 400 mg Single dose ibuprofen 400 mg capsule	Drug: Ibuprofen 400 mg Ibuprofen 400 mg as powder in gelatine capsules, single dose Other Names: M01A E01 Ibuprofen
Active Comparator: Ibuprofen 600 mg Single dose ibuprofen 600 mg capsule	Drug: Ibuprofen 600 mg Ibuprofen 600 mg as powder in gelatine capsules, single dose Other Names: M01A E01 Ibuprofen
Active Comparator: Ibuprofen 800 mg Single dose ibuprofen 800 mg capsule	Drug: Ibuprofen 800 mg Ibuprofen 800 mg as powder in gelatine capsules, single dose Other Names: M01A E01 Ibuprofen
Active Comparator: Paracetamol 500 mg Paracetamol 500 mg (acetaminophen) capsule	Drug: Paracetamol (acetaminophen) 500 mg Paracetamol (acetaminophen) 500 mg as powder in gelatine capsules, single dose Other Names: N02B E01 Paracetamol (acetaminophen)
Active Comparator: Paracetamol 1000 mg Single dose paracetamol 1000 mg (acetaminophen) capsule	Drug: Paracetamol (acetaminophen) 1000 mg Paracetamol (acetaminophen) 1000 mg as powder in gelatine capsules, single dose Other Names: N02B E01 Paracetamol (acetaminophen)
Active Comparator: Paracetamol 1000 mg + codeine 60 mg Single dose paracetamol (acetaminophen) 1000 mg + codeine 60 mg capsule	Drug: Paracetamol (acetaminophen) 1000 mg + codeine 60 mg Paracetamol (acetaminophen) 1000 mg + codeine 60 mg as powder in gelatine capsules, single dose Other Names: N02B E01 Paracetamol (acetaminophen) + R05D A04 codeine

Outcome Measures

Primary Outcome Measures

Sum Pain Intensity Score(SPI) [3 hour observation period]

Secondary Outcome Measures

Sum Pain Intensity Difference Score (SPID) [3 hours]
Sum Pain Intensity Score (SPI) [6 hours]
Sum Pain Intensity Difference Score (SPID) [6 hours]
Maximum Pain Intensity Difference Score (MAXPID) [Unknown, calculated variable]
Time to Maximum Pain Intensity Difference Score [Unknown, calculated variable]
Self-reported Occurrence of Adverse Effects [3 hours]
Self-reported Occurrence of Adverse Effects [6 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Oral and Maxillofacial Surgery, Ullevaal University Hospital	Oslo		Norway	N-0407

Sponsors and Collaborators

Ullevaal University Hospital
University of Oslo

Investigators

Study Chair: Lasse A Skoglund, DDS, DSCi, Section of Dental Pharmacology and Pharmacotherapy, ICD, Faculty of Dentistry, University of Oslo, POB 1119 Blindern, N-0317 Oslo, Norway
Study Director: Per Skjelbred, MD, DDS, PhD, Department of Oral and Maxillofacial Surgery, Ullevaal University Hospital, Kirkeveien 166, N-0407 Oslo, Norway
Principal Investigator: Gaute Lyngstad, DDS, Section of Dental Pharmacology and Pharmacotherapy, ICD, Faculty of Dentistry, University of Oslo, POB 1119 Blindern, N0317 Oslo, Norway