Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.

Hydromorphone is an alternative to morphine for Intrathecal Drug Delivery System (IDDS) to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥ 50% pain relief. The noninferiority margin (NIm) was defined as -0.15. Other outcomes included daily visual analog scale (VAS) score, breakthrough pain (BTP) incidence, intrathecal dose change and PCA bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased VAS scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM -3.33% vs ITMO 35.4%, P < .01, t-test) from the third week. The PCA bolus change rate was lower in the ITHM group than in the ITMO group (ITHM - 19.88% vs ITMO 7.79%, P < .01, t-test) from first week. Our result shows that intrathecal hydromorphone is noninferior to intrathecal morphine on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling breakthrough pain.