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; 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 Turner; Rob Vanderwaal; April Wareham; Eilish Gilvarry; Luke Mitcheson

doi:10.1186/s13063-022-06595-0

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^*, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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 language	English
Article number	697
Journal	Trials
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13063-022-06595-0
Publication status	Published - Dec 2022

Keywords

Extended-release buprenorphine
Long-acting injectable buprenorphine
Opioid use disorder
Psychosocial intervention
Randomised controlled trial

Access to Document

10.1186/s13063-022-06595-0

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

Marsden, J., Kelleher, M., Hoare, Z., Hughes, D., Bisla, J., Cape, A., Cowden, F., Day, E., Dewhurst, J., Evans, R., Hearn, A., Kelly, J., Lowry, N., McCusker, M., Murphy, C., Murray, R., Myton, T., Quarshie, S., Scott, G., ... Mitcheson, L. (2022). 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. Trials, 23(1), Article 697. https://doi.org/10.1186/s13063-022-06595-0

@article{dcbb5ac100c3406ea92bc2f5307c029d,

title = "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.",

keywords = "Extended-release buprenorphine, Long-acting injectable buprenorphine, Opioid use disorder, Psychosocial intervention, Randomised controlled trial",

author = "John Marsden and Mike Kelleher and Zo{\"e} Hoare and Dyfrig Hughes and Jatinder Bisla and Angela Cape and Fiona Cowden and Edward Day and Jonathan Dewhurst and Rachel Evans and Andrea Hearn and Joanna Kelly and Natalie Lowry and Martin McCusker and Caroline Murphy and Robert Murray and Tracey Myton and Sophie Quarshie and Gemma Scott and Sophie Turner and Rob Vanderwaal and April Wareham and Eilish Gilvarry and Luke Mitcheson",

note = "Funding Information: This protocol paper represents independent, investigator-initiated research at King{\textquoteright}s College London and South London & Maudsley NHS Trust, Bangor University, and collaborating NHS hospitals: Northumberland, Tyne & Wear NHS Foundation Trust; Birmingham & Solihull Mental Health NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust and Dundee Drug & Alcohol Recovery Service. The authors wish to thank Rosemarie Delaney, Frank Gray, and Bret Ryder (Indivior UK) for their comments on the first draft of the manuscript. The views expressed in this article are the authors and are not necessarily those of the funder or sponsor. KCL and SLaM hold the study indemnity insurance policy. The study PIS details the complaints and compensation procedure. The authors wish to thank the members of the study oversight committees: TSC: Prof. Richard Holland, Head of Leicester Medical School and Professor of Public Health Medicine (Chair); Steve Taylor, Programme Manager, Public Health England; Martin McCusker, Patient Representative; Jenny Bearn, Consultant Psychiatrist, Independent Advisor; Rory Gray, Senior Commissioning Officer Primary Care, Substance Misuse & Homeless Health; Lambeth Council and Christopher D'Souza, Lead Commissioner Substance Misuse, Primary Care and Homeless Health. DMC: Tim Millar, Professor of Substance Use and Addictions, University of Manchester (DMC Chair); Simon Skene, Professor of Medical Statistics, Director of Surrey Clinical Trials Unit and Clinical Research Facility (Independent Statistician); Dr John Dunn, Consultant in Addiction Psychiatry, Camden Specialist Drug Treatment Service (Independent Clinician); Paul Lennon (Patient Representative); and April Wareham (Public Representative). Funding Information: EXPO is investigator led. Research costs are supported by Indivior (the funder). Indivior will provide BUP-XR for the study. Indivior will be invited to comment on drafts of the protocol, SAP and HEAP, and study products, but will have no role in the data analysis and interpretation, the writing of reports, and the decision to submit reports for publication. King{\textquoteright}s College London (KCL) and South London and Maudsley (SLaM) NHS Trust are the study sponsors and hold the indemnity insurance policy. The sponsor{\textquoteright}s representative is Amy Holton, Quality Manager, KHP-CTO, London. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13063-022-06595-0",

language = "English",

volume = "23",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

number = "1",

}

Marsden, J, Kelleher, M, Hoare, Z, Hughes, D, Bisla, J, Cape, A, Cowden, F, Day, E, Dewhurst, J, Evans, R, Hearn, A, Kelly, J, Lowry, N, McCusker, M, Murphy, C, Murray, R, Myton, T, Quarshie, S, Scott, G, Turner, S, Vanderwaal, R, Wareham, A, Gilvarry, E & Mitcheson, L 2022, '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', Trials, vol. 23, no. 1, 697. https://doi.org/10.1186/s13063-022-06595-0

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. / Marsden, John; Kelleher, Mike; Hoare, Zoë et al.
In: Trials, Vol. 23, No. 1, 697, 12.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Extended-release pharmacotherapy for opioid use disorder (EXPO)

T2 - 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

AU - Marsden, John

AU - Kelleher, Mike

AU - Hoare, Zoë

AU - Hughes, Dyfrig

AU - Bisla, Jatinder

AU - Cape, Angela

AU - Cowden, Fiona

AU - Day, Edward

AU - Dewhurst, Jonathan

AU - Evans, Rachel

AU - Hearn, Andrea

AU - Kelly, Joanna

AU - Lowry, Natalie

AU - McCusker, Martin

AU - Murphy, Caroline

AU - Murray, Robert

AU - Myton, Tracey

AU - Quarshie, Sophie

AU - Scott, Gemma

AU - Turner, Sophie

AU - Vanderwaal, Rob

AU - Wareham, April

AU - Gilvarry, Eilish

AU - Mitcheson, Luke

N1 - Funding Information: This protocol paper represents independent, investigator-initiated research at King’s College London and South London & Maudsley NHS Trust, Bangor University, and collaborating NHS hospitals: Northumberland, Tyne & Wear NHS Foundation Trust; Birmingham & Solihull Mental Health NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust and Dundee Drug & Alcohol Recovery Service. The authors wish to thank Rosemarie Delaney, Frank Gray, and Bret Ryder (Indivior UK) for their comments on the first draft of the manuscript. The views expressed in this article are the authors and are not necessarily those of the funder or sponsor. KCL and SLaM hold the study indemnity insurance policy. The study PIS details the complaints and compensation procedure. The authors wish to thank the members of the study oversight committees: TSC: Prof. Richard Holland, Head of Leicester Medical School and Professor of Public Health Medicine (Chair); Steve Taylor, Programme Manager, Public Health England; Martin McCusker, Patient Representative; Jenny Bearn, Consultant Psychiatrist, Independent Advisor; Rory Gray, Senior Commissioning Officer Primary Care, Substance Misuse & Homeless Health; Lambeth Council and Christopher D'Souza, Lead Commissioner Substance Misuse, Primary Care and Homeless Health. DMC: Tim Millar, Professor of Substance Use and Addictions, University of Manchester (DMC Chair); Simon Skene, Professor of Medical Statistics, Director of Surrey Clinical Trials Unit and Clinical Research Facility (Independent Statistician); Dr John Dunn, Consultant in Addiction Psychiatry, Camden Specialist Drug Treatment Service (Independent Clinician); Paul Lennon (Patient Representative); and April Wareham (Public Representative). Funding Information: EXPO is investigator led. Research costs are supported by Indivior (the funder). Indivior will provide BUP-XR for the study. Indivior will be invited to comment on drafts of the protocol, SAP and HEAP, and study products, but will have no role in the data analysis and interpretation, the writing of reports, and the decision to submit reports for publication. King’s College London (KCL) and South London and Maudsley (SLaM) NHS Trust are the study sponsors and hold the indemnity insurance policy. The sponsor’s representative is Amy Holton, Quality Manager, KHP-CTO, London. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Extended-release buprenorphine

KW - Long-acting injectable buprenorphine

KW - Opioid use disorder

KW - Psychosocial intervention

KW - Randomised controlled trial

UR - http://www.scopus.com/inward/record.url?scp=85137001863&partnerID=8YFLogxK

U2 - 10.1186/s13063-022-06595-0

DO - 10.1186/s13063-022-06595-0

M3 - Article

C2 - 35986418

AN - SCOPUS:85137001863

SN - 1745-6215

VL - 23

JO - Trials

JF - Trials

IS - 1

M1 - 697

ER -

Marsden J, Kelleher M, Hoare Z, Hughes D, Bisla J, Cape A et al. 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. Trials. 2022 Dec;23(1):697. doi: 10.1186/s13063-022-06595-0

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

Keywords

Access to Document

Other files and links

Fingerprint

Cite this