PaSo paracetamol with strong opioids trial: paracetamol versus placebo in conjunction with strong opioids for cancer pain—a pilot randomised placebo-controlled withdrawal trial

Objectives Clinical guidelines, including the WHO analgesic ladder, advocate paracetamol in conjunction with strong opioids for moderate to severe cancer pain despite a lack of evidence for its efficacy in this setting. This pilot study aimed to evaluate the feasibility of a larger randomised controlled trial (RCT) with the aim of establishing whether paracetamol combined with strong opioids provides superior analgesia for cancer-related pain over strong opioids alone. Methods Adult patients with incurable cancer taking regular paracetamol and strong opioids with an average pain score 2–8 on a Numeric Rating Scale (NRS 0–10) in the past 24 hours were randomised to receive either paracetamol or placebo for 13 days, with assessments at day 7 and 14. Outcomes were recruitment, retention, appropriateness of study design, patient acceptability and early signals of pain outcome. Results Thirty-four participants were recruited and 28 randomised at 12 months. After 7 months, the intervention phase was reduced to 7 days to improve recruitment and mitigate attrition. Retention was high but the clinical team assessed 7 days in the study as adequate and less burdensome for the patients. Average pain (NRS) on day 7 (change from baseline) was similar in the placebo group (−0.27) versus the paracetamol group (−0.46). Groups difference: −0.19, 95% CI −1.1 to 0.7, ( p =0.67). Patient recruitment was slow. Due to this, the study did not progress to a definitive RCT. Conclusion This pilot study demonstrates feasibility of the withdrawal design but signalled the need for a different recruitment strategy and a shorter study. Notably, there were no adverse pain outcomes, as NRS scores and opioid requirements didn’t increase. Trial registration number NCT02706769 .