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

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.

Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation

“…The EXPO trial protocol has been published. 16 There is emergent qualitative literature on extendedrelease MOUD. Published evaluations include a qualitative study from Norway with 13 patients that have received one to four doses of extended-release naltrexone (an opioid antagonist) explored reasons for discontinuing treatment .…”

“…Secondary outcome measures include time enrolled in treatment, days abstinent from cocaine and illicit/non-medical benzodiazepines, and craving for heroin and cocaine. The EXPO trial protocol has been published 16…”

The FASTER-BUP Study, Extended-Release Injectable Buprenorphine for the Treatment of Opioid Use Disorder Among Individuals at High Risk of Overdose: Protocol for an Observational Prospective Study

“…14 Some real-world evidence studies of XR-BUP are also starting to emerge. 15,16 Notably, a pragmatic multicentre randomized controlled trial evaluating the effectiveness of XR-BUP compared to SL-BUP and methadone is underway in England and Scotland. 16 Despite its demonstrable efficacy, XR-BUP remains an understudied and underutilized tool with limited programs existing in Canada.…”

“…15,16 Notably, a pragmatic multicentre randomized controlled trial evaluating the effectiveness of XR-BUP compared to SL-BUP and methadone is underway in England and Scotland. 16 Despite its demonstrable efficacy, XR-BUP remains an understudied and underutilized tool with limited programs existing in Canada. In 2018, Health Canada approved one formulation of XR-BUP (ie, Sublocade TM ).…”

“…14 Some real-world evidence studies of XR-BUP are also starting to emerge. 15,16 Notably, a pragmatic multicentre randomized controlled trial evaluating the effectiveness of XR-BUP compared to SL-BUP and methadone is underway in England and Scotland. 16…”