BACKGROUND: Sublingual buprenorphine (BUP-SL) and liquid methadone (MET) and are the standard-of-care (SOC), daily maintenance medications for the treatment of opioid use disorder (OUD). A sizable proportion of the OUD treatment population does not adhere to treatment and achieve desired clinical benefit. Two promising therapeutic technologies address this deficit: new medication formulations and psychosocial interventions (PSI). This study will determine: (A) the effectiveness and cost-effectiveness – monthly injectable, extended-release (BUP-XR) a novel formulation in a head-to-head comparison with BUP-SL or MET; and (B) the effectiveness of BUP-XR with PSI versus BUP-SL or MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, four-arm, parallel group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five specialist National Health Service community treatment programmes in England and Scotland. In all sites, participants will be randomly allocated (1:1) to BUP-XR and BUP-SL or MET. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI and BUP-SL or MET with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from all non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR and BUP-SL or MET comparison. Using the same planning parameters, 300 participants are needed for the comparison of BUP-XR and BUP-SL or MET with PSI. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL or MET, and with an adjunctive personalised PSI. If there is evidence for the superiority of BUP-XR over SOC, this will have substantial implications for clinical practice and OUD treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register (number: 2018-004460-63).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.