A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis

Abstract

Objective: To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis.

Methods: Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months.

Results: Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment.

Conclusion: CR tramadol is effective for the management of painful osteoarthritis.

Figure 1)

Study design and patient disposition. AE Adverse events; CR Controlled-release

Figure 2)

Mean visual analogue score (VAS) pain intensities for the last week of treatment (diary scores). *P=0.0009 between treatments; ^†P=0.0001; ^‡P=0.0244 decrease from baseline. CR Controlled-release

Figure 3)

Western Ontario and McMaster Universities osteoarthritis index during the last week of treatment. *P=0.0007 between treatments; ^†P=0.0205 between treatments; ^‡P=0.0001 decrease from baseline. CR Controlled-release; VAS Visual analogue scores

Figure 4)

Short-form 36 Health Survey during the last week of treatment (per protocol population). Higher scores indicate a better health state. Data normalized to the Canadian population. *P≤0.0262 between treatments; ^†P≤0.0357 change from baseline. CR Controlled-release