Protocol of a randomised controlled trial: comparing the safety and efficacy of two methadone conversion strategies in Chinese patients with cancer pain receiving high-dose opioids

Introduction China has the highest global burden of new cancer diagnoses and cancer-related mortality, with approximately 60%–85% of patients with advanced malignancies experiencing moderate-to-severe pain. Although the WHO’s analgesic ladder is widely implemented, approximately 20% of cancer-related pain remains refractory. This persistent pain is often further complicated by opioid-induced side effects and the risk of opioid use disorders. Methadone, a potent opioid with distinct pharmacokinetic and pharmacodynamic properties, has shown potential in managing refractory cancer pain; however, there is a lack of standardised and evidence-based protocols for methadone conversion, particularly in patients requiring high-dose opioids. Methods and analysis This multicentre, open-label randomised controlled trial will enrol 164 Chinese patients with cancer and oral morphine equivalent daily dose requirements of ≥300 mg. Participants will be randomised to receive either the 3 day switch (3DS) strategy or the National Comprehensive Cancer Network (NCCN)-recommended methadone conversion method. The primary endpoints include time to stable analgesia, methadone conversion efficiency and overall pain relief rate. Secondary endpoints will evaluate pain intensity, frequency of breakthrough pain, corrected QT interval changes, incidence of adverse events and health-related quality of life. This trial is designed to generate high-quality clinical evidence to inform methadone conversion strategies for patients with refractory cancer pain who are dependent on high-dose opioids. By addressing existing gaps in clinical practice and pharmacoeconomic decision-making, the study aims to support the development of standardised methadone protocols. Ethics and dissemination This study was approved by the Medical Ethics Committee of Zhejiang Cancer Hospital (approval number: IRB-2024-314(IIT)) on 3 April 2024 and registered with the Chinese Clinical Trial Registry (ChiCTR2400085332) on 5 June 2024. The outcomes will be disseminated through national and international presentations and peer-reviewed publications. Trial registration number ChiCTR2400085332.