Extended-release pharmacotherapy for opioid use disorder (EXPO): Protocol for an open-label randomised controlled trial of injectable maintenance buprenorphine with personalised psychosocial intervention.

Abstract

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).