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Pain, PostoperativePhase 4NCT00921700

Analgesic Effect of Paracetamol, Paracetamol + Codeine, Ibuprofen and Their Combination

A Phase 4 study testing Ibuprofen + Paracetamol, Ibuprofen + Paracetamol + Codeine and Paracetamol + Codeine in people with Pain, Postoperative, run by Ullevaal University Hospital at 1 site in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 30 years
Conditions the study is for
Pain, Postoperative
What is being tested?
Ibuprofen + Paracetamol, Ibuprofen + Paracetamol + Codeine and Paracetamol + Codeine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
200 participants
Where
1 siteNorway
Study dates
Jun 2009to Apr 2015
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 30 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Norway1 site

  • Ullevaal University Hospital

    Oslo, NO-0407

Other trials in Norway

About this study

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

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.

Read the 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.

Being tested
Ibuprofen + Paracetamol, Ibuprofen + Paracetamol + Codeine, Paracetamol + Codeine, Placebo
Keywords
Paracetamol, Acetaminophen, Ibuprofen, Pain, Postoperative pain, third molar
Medical subject headings
Pain, Postoperative, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ibuprofen + ParacetamolDrug

    Also called Ibuprofen, ATC code: M01A E01, Paracetamol (Acetaminophen), ATC code: N02B E01

    Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg in gelatine capsules

  • Ibuprofen + Paracetamol + CodeineDrug

    Also called Ibuprofen, ATC code: M01A E01, Paracetamol (Acetaminophen), ATC code: N02B E01

    Single oral dose of ibuprofen 400 mg combined with paracetamol (acetaminophen) 1000 mg and codeine 60 mg in gelatine capsules

  • Paracetamol + CodeineDrug

    Also called Paracetamol (Acetaminophen), ATC code: N02B E01, Codeine, ATC code: R05D A04

    Single oral dose of paracetamol (acetaminophen) 1000 mg combined with codeine 60 mg in gelatine capsules

  • PlaceboDrug

    Also called Lactose, CAS No: 63-42-3

    Single oral dose of lactose as placebo in gelatine capsules

Study groups in NCT00921700
Study groupRoleWhat they receive
Ibuprofen + ParacetamolExperimentalSingle oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg
Receives: Drug: Ibuprofen + Paracetamol
Ibuprofen + Paracetamol + CodeineExperimentalSingle oral dose of ibuprofen 400 mg + paracetamol (acetaminophen) 1000 mg + codeine 60 mg
Receives: Drug: Ibuprofen + Paracetamol + Codeine
Paracetamol + CodeineActive comparatorSingle oral dose of paracetamol (acetaminophen) 1000 mg + codeine 60 mg
Receives: Drug: Paracetamol + Codeine
PlaceboPlacebo comparatorSingle oral dose of lactose as placebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Sum pain intensity SPI (0-10 Numerical Rating Scale)

    Measured: 6 hours

Secondary outcomes (3)

  1. Sum pain intensity difference score (PID)

    Measured: 6 hours

  2. Overall assessment of efficacy (4-point Verbal Rating Scale)

    Measured: 6 hours

  3. Adverse effects AE (Specific reporting of AE - type, duration and severity)

    Measured: 6 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionNov 2014
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00921700
Sponsor's protocol ID
PARIBU-022
Other IDs
EUDRACT No. 2007-001778-10
Status last verified
Mar 2016
First submitted
15 Jun 2009
Last updated
30 Mar 2016
Results posted
No
Data monitoring committee
No

Publications

  • Seideman P. Additive effect of combined naproxen and paracetamol in rheumatoid arthritis. Br J Rheumatol. 1993 Dec;32(12):1077-82. doi: 10.1093/rheumatology/32.12.1077.

    PubMed 8252318

  • Seideman P, Samuelson P, Neander G. Naproxen and paracetamol compared with naproxen only in coxarthrosis. Increased effect of the combination in 18 patients. Acta Orthop Scand. 1993 Jun;64(3):285-8. doi: 10.3109/17453679308993626.

    PubMed 8322582

  • Breivik EK, Barkvoll P, Skovlund E. Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study. Clin Pharmacol Ther. 1999 Dec;66(6):625-35. doi: 10.1053/cp.1999.v66.103629001.

    PubMed 10613619

  • Romsing J, Moiniche S, Dahl JB. Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia. Br J Anaesth. 2002 Feb;88(2):215-26. doi: 10.1093/bja/88.2.215.

    PubMed 11878655

  • Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth. 2002 Feb;88(2):199-214. doi: 10.1093/bja/88.2.199.

    PubMed 11878654

  • Skoglund LA, Skjelbred P, Fyllingen G. Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain. Pharmacotherapy. 1991;11(5):364-9.

    PubMed 1745622

  • Lyngstad G, Skjelbred P, Swanson DM, Skoglund LA. Analgesic effect of oral paracetamol 1000 mg/ibuprofen 400 mg, paracetamol 1000 mg/codeine 60 mg, paracetamol 1000 mg/ibuprofen 400 mg/codeine 60 mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study. Eur J Clin Pharmacol. 2023 Aug;79(8):1131-1141. doi: 10.1007/s00228-023-03525-0. Epub 2023 Jun 22.

    PubMed 37349498

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ibuprofen + Paracetamol, Ibuprofen + Paracetamol + Codeine and Paracetamol + Codeine in people with Pain, Postoperative, run by Ullevaal University Hospital at 1 site in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sum pain intensity SPI (0-10 Numerical Rating Scale) (time frame: 6 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00921700, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2016.

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