A Comparison of the Analgesic Efficacy of Tramadol Contramid OAD Versus Placebo in Patients with Pain Due to Osteoarthritis

Abstract

One thousand twenty-eight (1,028) patients with pain due to osteoarthritis (OA) of the knee were enrolled in this multicenter, randomized, double-blind, parallel study designed to assess the analgesic efficacy and safety of Tramadol Contramid OAD compared to placebo. An open-label phase was followed by a double-blind phase, in which a total of 646 patients were randomized to double-blind treatment with placebo or Tramadol Contramid OAD. Patients were titrated to their optimal dose (200mg or 300 mg), which was maintained for 12 weeks. An absolute mean reduction of 3.0+/-2.1 on a Pain Intensity Numerical Rating Scale (PI-NRS) was noted in the Tramadol Contramid OAD treatment group. The difference between active and placebo groups regarding this absolute mean reduction was statistically significant (P<0.001) throughout the study. The responder analysis demonstrated that a significantly greater percentage of patients in the active treatment arm achieved a reduction of >or=1 and >or=2 points on the PI-NRS score by the end of the study (P=0.035). A significantly greater percentage of respondents in the Tramadol Contramid OAD group indicated improvement on both the Patient and Physician Global Impressions of Change (P=0.0002). Both the 200mg and 300 mg doses contributed to the overall superiority of Tramadol Contramid OAD. The most frequent adverse events were consistent with the known side effects of tramadol and were generally mild to moderate in intensity. These results confirm that Tramadol Contramid OAD given once daily is an efficacious and safe treatment for pain due to OA.

Meta-analysis of dropout rates in randomized controlled clinical trials

“…The wash out of all analgesics including nonopioids may change the efficacy of opioids in osteoarthritis [2,5,10,11,12,18,19,24,27,34]. However, in a subgroup analysis we found only a statistically nonsignificant trend to decreased total dropouts in studies with nonsteriodal antiinflammatory drugs.…”

“…Another problem in the handling of dropouts can result from an open-label run-in phase [5], because nonresponders to opioids may drop out before the start of the trial period. Although dose titration was conducted after randomization in most trials in this meta-analysis, the dropout rate might be even higher in a real world setting.…”

“…A total of 22 publications were retrieved for more detailed evaluation [2,5,6,7,8,9,10,11,12,15,18,19,20,22,23,24,27,29,31,32,34,36,40]. Three were excluded because of double publication [36] or lack of data for our analysis (.…”

“…Diagnosis was confirmed using a standard set of clinical symptoms (i.e., American College of Rheumatology (ACR) criteria grades I-III) and radiographic signs. Some investigators included only osteoarthritis of the knee [2,5,6,10,11,18]. Others included osteoarthritis and other pain locations as well [23,29].…”

Immunosuppressive Effects of Opioids—Clinical Relevance

“…The majority of trials did not report any infectious complications (Roth et al 2000;Caldwell et al 2002;Raja et al 2002;Watson et al 2003;Babul et al 2004;Hale et al 2005;Matsumoto et al 2005;Gana et al 2006;Kivitz et al 2006;Hale et al 2007;Beaulieu et al 2008;Gordon et al 2010). Only 6 out of 18 trials reported infectious complications but their incidence was too low to detect statistically significant differences (see Table 3; (Gimbel et al 2003;Markenson et al 2005;Langford et al 2006;Burch et al 2007;Katz et al 2007;O'Donnell et al 2009). Thus, these data do not permit any firm conclusions regarding the influence of opioids on the development of infectious complications.…”