Maxi-Analgesic Osteoarthritis (OA) Study
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|ClinicalTrials.gov Identifier: NCT01420666|
Recruitment Status : Withdrawn (The study was withdrawn for administrative reason)
First Posted : August 22, 2011
Last Update Posted : January 6, 2016
|Condition or disease||Intervention/treatment||Phase|
|Osteoarthritis||Drug: Acetaminophen Drug: Maxigesic 325 Drug: Ibuprofen Drug: Placebo||Phase 3|
Osteoarthritis is a significant and disabling disease in the developed world.
Published guidelines for medical management of osteoarthritis from expert groups, in general advocate acetaminophen as first line treatment. The European League Against Rheumatism (EULAR) guidelines (1)recommend acetaminophen should be first choice therapy in OA, and that NSAIDs should be reserved for those patients unresponsive to acetaminophen. The American College of Rheumatology Guidelines (2) recommend acetaminophen be considered as reasonable initial therapy in patients with mild to moderate OA pain and that NSAIDs be considered as an initial alternative in moderate to severe OA pain. The Canadian guidelines recommend acetaminophen for mild OA pain and NSAIDs for moderate to severe OA (3).
A Cochrane Review of acetaminophen in osteoarthritis concluded that NSAIDs were superior to acetaminophen for improving knee and hip pain in people with OA. However, it was noted that the size of the treatment effect was modest with NSAIDs appearing to be more effective in OA subjects with moderate-to-severe pain (4).
There are many situations in clinical practice where either acetaminophen alone or low dose ibuprofen is not sufficiently effective. In these cases the dose of acetaminophen cannot be increased to more than 4000mg/day due to toxicity concerns. In the case of ibuprofen the dose can be increased from 1200mg/day to 2400mg/day. However comparison of low dose ibuprofen with high dose showed gastrointestinal (GI) toxicity increased: the relative risk (RR) of GI complications increased from 1.6 (95% CI 0.8, 3.2) with low dose ibuprofen to 4.2 (95% CI 1.8, 9.8) with high dose ibuprofen (5). Ibuprofen is associated with a low risk of serious gastrointestinal complications, but this advantage is probably lost at doses above 1800 mg/day (6).
A simple combination treatment whereby both acetaminophen and ibuprofen can be taken together as one single tablet and at the same time each day would, if effective, have the advantage of increasing analgesia without having to raise the ibuprofen dose above 1200mg/day (1170mg if administered every 6 hours) and lose the improved safety profile associated with a lower dose of ibuprofen.
- Pendleton A, Arden N, Dougados M, Doherty M, Bannwarth B, Bijlsma JW, et al. EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis. 2000;59(12):936-44.
- Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43(9):1905-15.
- Tannenbaum H, Peloso PM, Russell AS, Marlow B. An evidence-based approach to prescribing NSAIDs in the treatment of osteoarthritis and rheumatoid arthritis: The Second Canadian Consensus Conference. Can J Clin Pharmacol. 2000;7 Suppl A:4A-16A.
- Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006(1):CD004257.
- Henry D, Lim LLY, Garcia Rodriguez LA, Perez Gutthann S, Carson JL, Griffin M, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: Results of a collaborative meta-analysis. British Medical Journal. 1996;312 (7046):1563-6.
- Henry D, McGettigan P. Epidemiology overview of gastrointestinal and renal toxicity of NSAIDs. Int J Clin Pract Suppl. 2003;Supplement.(135):43-9.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Maxi-Analgesic OA Study: Multicentre, Double-blind, Placebo-controlled, Randomized, Parallel Group Comparison of the Effects of Maxigesic 325 With Acetaminophen or Ibuprofen on Patients With Pain From Osteoarthritis|
Active Comparator: Maxigesic 325
Maxigesic 325 (acetaminophen 325 mg + ibuprofen 97.5mg), three tablets four times a day, orally, with food
Drug: Maxigesic 325
Maxigesic 325 (Acetaminophen 325 mg+ ibuprofen 97.5mg), three tablets four times a day, orally, with food
Other Name: Actaminophen/paracetamol + ibuprofen
Active Comparator: Acetaminophen
Acetaminophen 325 mg, three tablets four times a day, orally, with food
Acetaminophen 325 mg, three tablets four times a day, orally, with food
Other Name: Paracetamol
Active Comparator: Ibuprofen
ibuprofen 97.5mg, three tablets four times a day, orally, with food
Ibuprofen 97.5mg, three tablets four times a day, orally, with food
Placebo Comparator: Placebo
placebo, three tablets four times a day, orally, with food
- WOMAC pain intensity VAS [ Time Frame: 13 weeks ]The difference between the week 13 average WOMAC pain intensity VAS and the baseline WOMAC VAS
- Time to peak analgesic effect [ Time Frame: 13 weeks ]Time to peak analgesic effect using the WOMAC VAS pain intensity score (the average pain intensity score of that week).
- Time-adjusted SPID [ Time Frame: 13 weeks ]Time adjusted SPID obtained from the mean weekly WOMAC VAS pain intensity assessments over 13 weeks
- Difference of WOMAC stiffness score [ Time Frame: 13 weeks ]Difference between the week 13 WOMAC stiffness score and the baseline WOMAC stiffness score
- Difference of WOMAC function score [ Time Frame: 13 weeks ]Difference between the week 13 WOMAC function score and the baseline WOMAC function score
- Time to rescue medication [ Time Frame: 13 weeks ]Tie to rescue medication (oxycodone)
- Safety [ Time Frame: 13 weeks ]Adverse events (serious and non-serious) will be assessed during the blinded study period and up to 30 days after the last dose of study medication. Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events) and known acetaminophen adverse effects (i.e. clinical evidence of hepatitis) will be compared between groups.
- Time-adjusted WOMAC stiffness score [ Time Frame: Over 13 weeks ]Time-adjusted WOMAC stiffness score over 13 weeks
- Time-adjusted WOMAC function score [ Time Frame: over 13 weeks ]Time-adjusted WOMAC function score over 13 weeks
- Patient global assessment [ Time Frame: 13 weeks ]A categorical global pain rating will be obtained weekly during the double blind treatment 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): NCT01420666
|Principal Investigator:||John Moodie, Doctor||Clinical Trial New Zealand Ltd, 32 Kahikatea Drive, Hamilton, New Zealand|