Analgesic efficacy and safety of tramadol/acetaminophen combination tablets (Ultracet®) in treatment of chronic low back pain:: A multicenter, outpatient, randomized, double blind, placebo controlled trial

Objective. To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg (tramadol/APAP) combination tablets for treatment of chronic low back pain (LBP). Methods. This 91 day, multicenter, outpatient, randomized, double blind, placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for greater than or equal to 3 months. Patients with at 19 least moderate pain [pain visual analog scale (VAS) with scores greater than or equal to 40/100 mm] after washout were randomized to tramadol/APAP or placebo. After 10 day titration, patients received 1 or 2 tablets QID. Primary outcome measure was final pain VAS score. Secondary measures included pain relief, quality of life and physical functioning, efficacy failure, and overall medication assessments. Results. In total, 336 intent-to-treat patients received tramadol/APAP (n = 167) or placebo (n = 169). Mean baseline pain VAS score was 67.8. Intent-to-treat analysis showed significantly better mean final pain VAS scores (47.4 vs 62.9; p < 0.001) and mean final pain relief scores (1.8 vs 0.7; p < 0.001) for tramadol/APAP than tor placebo. Roland Disability Questionnaire scores and physical-related subcategories of the McGill Pain Questionnaire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for traadol/APAP patients. More patients rated tramadol/APAP as "very good" or "good" than placebo (63.6 vs 25.2%; p < 0.001). Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9% (tramadol/APAP) vs 54.7% (placebo; p < 0.001). The most common treatment related adverse events with tramadol/APAP were nausea (12.0%), dizziness (10.8%), and constipation (10.2%). Average daily dose of tramadol/APAP was 4.2 tablets (tramadol 158 mg/APAP 1369 mg). Conclusion. Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction, in measures of physical functioning and quality of life, and in overall medication assessments, with a tolerability profile comparable with other opioids used for the treatment of chronic LBP.