401TiP - Oral opioid vs intravenous patient-controlled analgesia (PCA) with hydromorphone bolus-only or continuous infusion to maintain analgesia for severe cancer pain: A randomized phase III trial

Background

As reported in our previous study (Lin, JNCCN 2021) intravenous (i.v.) opioid titration with PCA provides earlier analgesia and higher patient satisfaction for pain control compared with conventional titration administrated by medical staff. After successful opioid titration, it is appropriate to maintain analgesia with regularly scheduled medication plus supplemental doses for breakthrough cancer pain (BTcP). Compared with regularly scheduled doses, continuous infusion using a PCA pump can confer a more stable and effective plasma concentration to control background pain. An on-demand bolus dose allows patients to voluntarily control BTcP. Therefore, continuous infusion plus an on-demand bolus dose may maximize the benefits of i.v. PCA (IPCA) for maintenance therapy. Our previous phase II study (Lin, JNCCN 2022) reported that IPCA was superior to oral administration as maintenance analgesia for severe cancer pain. IPCA with continuous infusion vs. without continuous infusion (bolus-only) may not be different in terms of pain control. IPCA without continuous infusion may consume less opioid. Therefore, in this study we aim to confirm these findings in a phase III study with a larger sample size.

Trial design

This is a multicenter open-label randomized controlled phase III trial. Eligibility criteria include: patients who are diagnosed with a malignant solid tumor by pathology or cytology and who have had persistent severe cancer-related pain (≥7 at rest on the 11-point Numeric Pain Rating Scale [NRS]); age 18 to 80 years; and ECOG PS≤3. Patients were randomly assigned in a 2:2:1 ratio to 1 of 3 arms: (A1) IPCA hydromorphone with bolus-only dose as needed (PRN); (A2) IPCA hydromorphone with continuous infusion for background pain plus bolus for BTcP; or (B) oral extended-release morphine around the clock for background pain and normal-release morphine PRN for BTcP. The primary endpoint was average NRS over days 1-3 (sum of previous 24-hour average pain scores for days 1–3 divided by 3). Enrollment is ongoing.

Clinical trial identification

NCT04785768.

Legal entity responsible for the study

The authors.

Funding

Guiding Project of Fujian Province (No.2023Y0057).

Disclosure

All authors have declared no conflicts of interest.