Oxycodone/naloxone PR versus oxycodone PR in advanced cancer: A multi-centre randomised trial (ENhANCE trial).

Background: Opioid-induced constipation is a common side effect of Oxycodone. Oxycodone/Naloxone Prolonged Release (OXN PR) mitigates opioid-induced constipation in non-cancer pain, however its evidence is limited in people with pain from advanced cancer.

Aims: To demonstrate analgesic non-inferiority, and superiority in reducing constipation for Oxycodone/Naloxone Prolonged Release (OXN PR) compared to Oxycodone Prolonged Release (Oxy PR).

Design: Multi-centre open-label randomised controlled trial comparing OXN PR to Oxy PR over 5 weeks. The primary aim was to demonstrate analgesic non-inferiority of OXN PR compared to Oxy PR. The secondary aim was to demonstrate superiority of constipation reduction in the OXN PR arm.

Setting/participants: Participants with moderate-severe pain (⩾4/10) from advanced cancer were eligible.

Results: Thirty seven of planned 96 patients were recruited with the study stopping early due to enrolment challenges during the COVID-19 pandemic. Average pain was -1.5 points (95% CI -3.3; 0.4) favouring the OXN PR arm compared to Oxy PR at 5 weeks, meeting analgesic non-inferiority, defined as falling within a one point non-inferiority margin. The OXN PR arm demonstrated less constipation with a significantly lower Bowel Function Index score (-24.87 (95% CI 47.54; 2.21), p = 0.03) compared to Oxy PR. Adverse effect safety profile favoured OXN PR.

Conclusions: OXN PR is non-inferior to Oxy PR in analgesic effectiveness and superior in reducing constipation. These results indicate OXN PR as the choice of opioid preparation in advanced cancer. Future studies may explore adding naloxone to other slow and immediate release opioid preparations.

Trial registry: Australian New Zealand Clinical Trials RegistryTrial registration number:ACTRN12619001282178URL of trial registry record:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377673&isReview=true.