Oxycodone/naloxone versus placebo for acute spinal pain in compliant participants: secondary analysis of a randomised clinical trial.

Abstract

A recent randomised controlled trial found that an oxycodone/naloxone combination was not effective at relieving acute back/neck pain compared with placebo. However, only half of the participants were compliant with the regimen. Therefore, the current study estimated treatment efficacy in participants who complied with the regimen. A complier average causal effect analysis was prespecified in the original trial's statistical analysis plan. It was performed using (i) a propensity-weighting approach, (ii) a joint modelling approach, and (iii) a propensity-matching approach, with compliance defined using different cut-off points (taking ≥20%, ≥40%, ≥60%, and ≥80% of the prescribed dose). The primary outcome was pain severity at week 6. Key secondary outcomes were pain severity at weeks 2, 4, 12, 26, and 52. A per-protocol analysis was also conducted at all time points. After propensity-weighting, a small but significant difference favouring the placebo group for pain severity was found at week 6 (mean difference, 0.78; 95% confidence interval, 0.22-1.33; P=0.006). Analysis using different approaches, pain outcomes at other time points, and sensitivity analysis using different cut-offs of compliance either favoured the placebo group or showed no difference between groups. This secondary analysis of a randomised controlled trial highlights the non-effectiveness of an oxycodone/naloxone combination in acute spinal pain compared with placebo, even when the population complies with the treatment regimen. These results, and the original study results, argue against the use of oxycodone/naloxone combinations for acute spinal pain. OPAL (ACTRN12615000775516).