Opioid-induced constipation (OIC) is a common side effect of Oxycodone. Oxycodone/Naloxone Prolonged Release (OXN PR) contains naloxone, which mitigates OIC as demonstrated in patients with chronic non-cancer pain. In palliative care, the use of OXN PR has raised concerns of analgesic efficacy and limited benefit in OIC. We aimed to demonstrate analgesic non-inferiority, and constipation superiority of OXN PR compared to Oxycodone Prolonged Release (Oxy PR).

 

This multi-centre open-label randomised controlled trial of OXN PR vs Oxy PR for cancer-related pain was conducted at 5 Australian sites. The primary outcome was average pain difference on Brief Pain Inventory-Short Form (BPI-SF) at 5 weeks. Prespecified equivalence margin was 1. Secondary outcomes were comparison of other pain outcomes (BPI-SF), constipation (Bowel Function Index, BFI), quality of life (EORTC-QLQ-C30), and opioid and laxative dose over 5 weeks. Intention to treat analysis was performed. Participants had moderate-severe pain (≥ 4/10), and no liver dysfunction.

 

37 of planned 96 patients were recruited with the study stopping early due to the pandemic, however outcomes were met with statistically significant results. 

Average pain was -1.5 lower (95% CI-3.3;.4) in the OXN PR arm compared to Oxy PR at 5 weeks, meeting analgesic non-inferiority.

Constipation scores were significantly better in the OXN PR arm, with mean difference in BFI -25 (95% CI -48;-2), p.03, meeting superiority. 

This occurred with the OXN PR group using a lower study drug dose and laxative doses.

 

OXN PR is analgesically non-inferior to Oxy PR, and superior in constipation outcomes. This is despite the OXN PR group requiring lower doses of study drug and lower laxative doses. These important results indicate OXN PR as the choice of opioid preparation in advanced cancer.