Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone

John Marsden (Lead / Corresponding author), Mike Kelleher, Zoë Hoare, Dyfrig Hughes, Jatinder Bisla, Angela Cape, Fiona Cowden, Edward Day, Jonathan Dewhurst, Rachel Evans, Andrea Hearn, Joanna Kelly, Natalie Lowry, Martin McCusker, Caroline Murphy, Robert Murray, Tracey Myton, Sophie Quarshie, Gemma Scott, Sophie TurnerRob Vanderwaal, April Wareham, Eilish Gilvarry, Luke Mitcheson

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    Abstract

    Background: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated.

    Methods: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from 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 versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. 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 and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere.

    Trial registration: EU Clinical Trials register 2018-004460-63.

    Original languageEnglish
    Article number697
    Number of pages19
    JournalTrials
    Volume23
    DOIs
    Publication statusPublished - 19 Aug 2022

    Keywords

    • Adult
    • Analgesics, Opioid/adverse effects
    • Buprenorphine/adverse effects
    • Cost-Benefit Analysis
    • Delayed-Action Preparations/therapeutic use
    • Humans
    • Methadone/adverse effects
    • Multicenter Studies as Topic
    • Narcotic Antagonists/adverse effects
    • Opioid-Related Disorders/drug therapy
    • Pragmatic Clinical Trials as Topic
    • Randomized Controlled Trials as Topic
    • State Medicine
    • Tablets/therapeutic use
    • Psychosocial intervention
    • Long-acting injectable buprenorphine
    • Opioid use disorder
    • Extended-release buprenorphine
    • Randomised controlled trial

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