Analgesic Effect of Paracetamol, Paracetamol + Codeine, Ibuprofen and Their Combination
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ClinicalTrials.gov Identifier: NCT00921700 |
Recruitment Status :
Completed
First Posted : June 16, 2009
Last Update Posted : March 30, 2016
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Condition or disease | Intervention/treatment | Phase |
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Pain, Postoperative | Drug: Ibuprofen + Paracetamol Drug: Ibuprofen + Paracetamol + Codeine Drug: Paracetamol + Codeine Drug: Placebo | Phase 4 |
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 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 |

Arm | Intervention/treatment |
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Experimental: Ibuprofen + Paracetamol
Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg
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Drug: Ibuprofen + Paracetamol
Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg in gelatine capsules
Other Names:
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Experimental: Ibuprofen + Paracetamol + Codeine
Single oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg + codeine 60 mg
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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:
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Active Comparator: Paracetamol + Codeine
Single oral dose of paracetamol (acetaminophen) 1000 mg + codeine 60 mg
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Drug: Paracetamol + Codeine
Single oral dose of paracetamol (acetaminophen) 1000 mg combined with codeine 60 mg in gelatine capsules
Other Names:
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Placebo Comparator: Placebo
Single oral dose of lactose as placebo
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Drug: Placebo
Single oral dose of lactose as placebo in gelatine capsules
Other Names:
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- Sum pain intensity SPI (0-10 Numerical Rating Scale) [ Time Frame: 6 hours ]
- Sum pain intensity difference score (PID) [ Time Frame: 6 hours ]
- Overall assessment of efficacy (4-point Verbal Rating Scale) [ Time Frame: 6 hours ]
- Adverse effects AE (Specific reporting of AE - type, duration and severity) [ Time Frame: 6 hours ]

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

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
Norway | |
Ullevaal University Hospital | |
Oslo, Norway, NO-0407 |
Study Director: | Lasse A Skoglund, DDS, DSci | University of Oslo | |
Principal Investigator: | Gaute Lyngstad, DDS | University of Oslo |
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 |
Paracetamol Acetaminophen Ibuprofen |
Pain Postoperative pain third molar |
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 |