Paracetamol is ineffective for acute low back pain even for patients who comply with treatment: complier average causal effect analysis of a randomized controlled trial

In 2014, the Paracetamol for Acute Low Back Pain (PACE) trial demonstrated that paracetamol had no effect compared with placebo in acute low back pain (LBP). However, noncompliance was a potential limitation of this trial. The aim of this study was to investigate the efficacy of paracetamol in acute LBP among compliers. Using individual participant data from the PACE trial (ACTN12609000966291), complier average causal effect (CACE), intention-to-treat, and per protocol estimates were calculated for pain intensity (primary), disability, global rating of symptom change, and function (all secondary) after 2 weeks of follow-up. Compliance was defined as intake of an average of at least 4 of the prescribed 6 tablets of regular paracetamol per day (2660 mg in total) during the first 2 weeks after enrolment. Exploratory analyses using alternative time points and definitions of compliance were conducted. Mean between-group differences in pain intensity on a 0 to 10 scale using the primary time point and definition of compliance were not clinically relevant (propensity-weighted CACE 0.07 [-0.37 to 0.50] P = 0.76; joint modelling CACE 0.23 [-0.16 to 0.62] P = 0.24; intention-to-treat 0.11 [-0.20 to 0.42] P = 0.49; per protocol 0.29 [-0.07 to 0.65] P = 0.12); results for secondary outcomes and for exploratory analyses were similar. Paracetamol is ineffective for acute LBP even for patients who comply with treatment. This reinforces the notion that management of acute LBP should focus on providing patients advice and reassurance without the addition of paracetamol.