Bolus-only versus bolus plus continuous infusion hydromorphone for refractory cancer pain: a prospective, multicenter, randomized noninferiority trial

Refractory cancer pain (RCP) remains difficult to manage despite guideline-based therapy. Patient-controlled intravenous analgesia (PCIA) is increasingly used, yet the optimal administration mode remains unclear. In this prospective, multicenter, randomized, non-inferiority trial, patients with refractory cancer pain were enrolled between December 1, 2018, and August 31, 2022, and randomly assigned to either a bolus-only PCIA group (Group B) or a bolus plus continuous infusion group (Group BC). Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary endpoint was the pain relief rate at 72 h after PCIA initiation, defined as the proportion of patients achieving a ≥ 50% reduction in resting pain intensity from baseline. Non-inferiority was evaluated using the 90% confidence interval (CI) for the between-group difference, with a predefined non-inferiority margin of − 10%. A total of 226 patients were randomized. with 104 assigned to Group B and 111 to Group BC. Both groups showed significant reductions in resting NRS scores and breakthrough cancer pain (BTcP) NRS scores from T1 to T6 compared with baseline (all P < 0.05). At 72 h, the pain relief rate was 89.4% in Group B and 94.2% in Group BC. The between-group difference yielded a 90% CI of − 11.2% to 1.1%, which crossed the predefined non-inferiority margin. Therefore, non-inferiority of Group B compared with Group BC was not demonstrated. The incidence of PCIA-related adverse events was comparable between the two groups. Non-inferiority of bolus-only PCIA compared with bolus plus continuous infusion was not established. Nevertheless, both PCIA administration modes provided effective analgesia and demonstrated favorable safety profiles in patients with refractory cancer pain. Chinese Clinical Trial Registry, ChiCTR1800020014. Registered 19 November 2018, https://www.chictr.org.cn/showprojEN.html?proj=32731