A 2-Week, multicenter, randomized, double-blind, double-dummy, add-on study of the effects of titration on tolerability of tramadol/acetaminophen combination tablet in Korean adults with knee osteoarthritis pain

Chan Bum Choi, Jung Soo Song, Young Mo Kang, Chang Hee Suh, Jisoo Lee, Jung Yoon Choe, Choong Ki Lee, Seung Cheol Shim, Won Tae Chung, Gwan Gyu Song, Hyun Ah Kim, Jong Dae Ji, Eon Jeong Nam, Sung Hoon Park, Young Hoon Hong, Dong Hyuk Sheen, Mi Kyoung Lim, Young II Seo, Yoon Kyoung Sung, Tae Hwan KimJong Tae Lee, Sang Cheol Bae

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Abstract

Background: Combined tramadol/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs. Objective: The aim of this study was to assess the effect of tramadol/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis. Methods: This 2-week, multicenter, randomized, double-blind, double-dummy, add-on study was conducted at 12 tertiary referral university hospitals in the Republic of Korea. Patients aged 35 to 75 years with knee osteoarthritis receiving a stable dose of NSAIDs and with a daily mean pain-intensity score of ≥4 on a numeric rating scale (NRS) (0 = no pain to 10 = worst pain) during the 48 hours prior to enrollment were eligible. Patients were randomly assigned to receive 1 tablet of tramadol/acetaminophen 37.5/325 mg QD and 1 placebo BID for 3 days, followed by 1 active tablet BID and 1 placebo QD for 4 days, followed by 1 active tablet TID for 7 days (titration group) or 1 tablet of combined tramadol 37.5 mg/acetaminophen 325 mg TID for 14 days (nontitration group). The primary outcome measure was the rate of treatment discontinuation due to AEs. Secondary outcome measures were time to discontinuation due to AEs, prevalences and characteristics of AEs, decrease from baseline in pain intensity as measured on the NRS, and change in the Korean version of the Western Ontario and McMaster Universities (K-WOMAC) index score (scale: 0 = best to 100 = worst). Results: A total of 250 patients were enrolled (92.0% female; mean [SD] age, 60.2 [7.8] years; mean [SD] weight, 60.0 [9.2] kg [range, 37.5-90.7 kg]; all Korean). The discontinuation rate was significantly lower in the titration group than in the nontitration group (10.5% vs 26.2%; P < 0.001). The Kaplan-Meier survival curve showed that the rates of discontinuation due to AEs were similar in the 2 groups up to day 2, but thereafter the discontinuation rate was significantly lower in the titration group. The most common AEs were nausea (12.1% and 24.6% in the titration and nontitration groups, respectively; P = 0.008), vomiting (4.0% and 17.2%; P < 0.001), and dizziness (9.7% and 22.1%; P = 0.005). No serious AEs were reported in either group. Tramadol/acetaminophen use was associated with a similar decrease from baseline in pain in both the titration and nontitration groups (mean [SD] Δ: NRS, -1.60 [1.62] vs -1.68 [1.58]; total K-WOMAC, -12.86 [13.73] vs -12.52 [16.58]). Conclusions: In this population of Korean patients with knee osteoarthritis pain managed with a stable dose of NSAIDs, titration of tramadol/acetaminophen over 12 days was associated with improved tolerability and a significantly lower discontinuation rate compared with nontitration. Both regimens significantly reduced from baseline associated with osteoarthritis.

Original languageEnglish
Pages (from-to)1381-1389
Number of pages9
JournalClinical Therapeutics
Volume29
Issue number7
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • acetaminophen
  • osteoarthritis
  • randomized controlled trial
  • tramadol

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Choi, C. B., Song, J. S., Kang, Y. M., Suh, C. H., Lee, J., Choe, J. Y., Lee, C. K., Shim, S. C., Chung, W. T., Song, G. G., Kim, H. A., Ji, J. D., Nam, E. J., Park, S. H., Hong, Y. H., Sheen, D. H., Lim, M. K., Seo, Y. II., Sung, Y. K., ... Bae, S. C. (2007). A 2-Week, multicenter, randomized, double-blind, double-dummy, add-on study of the effects of titration on tolerability of tramadol/acetaminophen combination tablet in Korean adults with knee osteoarthritis pain. Clinical Therapeutics, 29(7), 1381-1389. https://doi.org/10.1016/j.clinthera.2007.07.015