Clinical trial NCT05164549: Extended-release Pharmacotherapy for Opioid Use Disorder
Official title: Extended-release Pharmacotherapy for Opioid Use Disorder (EXPO): Protocol for an Open-label Randomised Controlled Trial of Injectable Maintenance Buprenorphine With Personalised Psychosocial Intervention.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opiate Substitution Treatment
Keywords: opiate
opioid
opioid treatment
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: South London and Maudsley NHS Foundation Trust
name: Greater Manchester Mental Health NHS Foundation Trust
name: Northumberland, Tyne and Wear NHS Foundation Trust
name: Birmingham and Solihull Mental Health NHS Foundation Trust
name: NHS Tayside
name: Bangor University
First posted: 2021-12-20
Enrollment: 342
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is a clinical superiority effectiveness contrast to standard of care. Reported following SPIRIT and CONSORT standards, the study will determine whether extended-release injectable depot Buprenorphine (XR-Bup) maintenance therapy for OUD over six months is clinically superior to standard-of-care, oral medication (sublingual Buprenorphine \[SL-Bup\] or oral methadone \[Met\]; together: Bup/Met)

Detailed description: EXPO is a pragmatic, multi-centre, open label, four-arm, parallel group, superiority RCT, with a qualitative (mixed-methods) evaluation. The objective of the study is to determine the effectiveness and cost-effectiveness of XR-BUP versus SOC SL-BUP or MET. The primary study endpoint is six months of study treatment. EXPO also contains a single-site evaluation of the effectiveness of XR-BUP with adjunctive PSI versus SOC with adjunctive PSI. Participants allocated to XR-BUP can request to receive longer-term treatment for the duration of the study.

The study population is adults (≥18 years) enrolled in standard-of-care medication treatment for OUD. The study setting is specialist community addiction treatment programmes operated by the National Health Service in England and Scotland. There will be five participant treatment sites in South-East England (South London); North-East England (Newcastle); West Midlands, England (Solihull and Wolverhampton); North-West England (Manchester), and Tayside, Scotland (Dundee).

Groups

In all sites, participants will be randomly allocated to one of two groups:

Group 1. Injectable medication for OUD for 24 weeks (XR-BUP; the experimental condition) Group 2. Oral medication for OUD for 24 weeks (SL-BUP or MET; the control condition).

At the EXPO co-ordinating centre in South London, there will also be random allocation of participants to two additional groups, as follows:

Group 3. Injectable medication for OUD with adjunctive PSI for 24 weeks (XR-BUP with PSI; the experimental condition)

Group 4. Oral medication for OUD with adjunctive PSI for 24 weeks (SL-BUP or MET with PSI; the control condition).

Study aims

Across 24-weeks of study treatment, the primary aim of the EXPO study is to determine:

1. The effectiveness and cost-effectiveness of XR-BUP versus SL-BUP or MET; and
2. The effectiveness of XR-BUP with PSI versus SL-BUP or MET with PSI.

Across 24-weeks of study treatment, secondary study aims will determine the:

1. Safety of XR-BUP;
2. Retention of XR-BUP; SL-BUP; MET; XR-BUP with PSI; and SL-BUP or MET with PSI;
3. Effectiveness of XR-BUP and SL-BUP and MET to reduce opioid craving;
4. Effectiveness of XR-BUP; SL-BUP; MET; XR-BUP with PSI; SL-BUP with PSI; and MET with PSI to reduce use of heroin, cocaine, and benzodiazepines;
5. Effectiveness of XR-BUP and SL-BUP and MET to improve social functioning and recovery.
6. Cost-effectiveness of XR-BUP versus SL-BUP and MET, based on the incremental cost per quality-adjusted life year (QALY) gained.

Study aims will be evaluated by following a pre-registered statistical and health economic analysis plan.

Eligibility criteria: IInclusion criteria

1. Aged ≥ 18 years (no upper age limit);
2. Current diagnosis of DSM-5 OUD via SCID-5-RV (moderate-severe at baseline for current episode);
3. Currently enrolled on Met (30mg/day or less) or sublingual Bup or Bup-NX (24mg/day or less) or Esp (18mg/day or less) and in the view of the clinician would be able to convert to XR-Bup within 7 days post randomisation;
4. Voluntarily seeking treatment and able to attend the clinic as required in the protocol;
5. Able to communicate in English to level required to accept standard care and psychosocial intervention;
6. Possession of a contactable personal mobile phone or landline telephone number and ability to nominate at least one locator individual with a verifiable address and a telephone number to assist with the arrangement of follow-up appointments;
7. Living circumstances judged to be of sufficient stability to be able to engage/adhere to the study protocol;
8. Is not pregnant (confirmed) or breast feeding and, if currently or intending to have potentially procreative intercourse, agrees to use a birth control method (either oral hormonal contraceptives, barrier \[condom or diaphragm\], or Nexplanon implant) for the duration of the study.

8.2 Exclusion criteria

1. Clinically significant medical condition or observed abnormalities on physical examination or laboratory investigation, including but not limited to:

   1. uncontrolled hypertension, significant heart disease (including angina and myocardial infarction in past 12 months), or any cardiovascular abnormality which is judged to be clinically significant;
   2. severe alcohol dependence/withdrawal syndrome which is judged to be clinically significant and may constitute a risk to the patient's safety;
   3. acute hepatitis taken as clinical jaundice on examination, or evidence of blood bilirubin level above the normal range for local reference criteria, or evidence of serum levels of aspartate aminotransferase, alanine aminotransferase levels that are more than three-times the upper limit of the normal range;
2. History of allergic or adverse reactions to Bup or the proprietary ATRIGEL delivery system for XR-Bup (Sublocade®)\*;
3. Clinically significant or uncontrolled mental health problems (including but not limited to psychosis, bipolar disorder, schizoaffective disorder), or history or evidence of organic brain disease or dementia that may compromise safety or compliance with the study protocol;
4. Current (past 30 day) suicide plan or suicide attempt in past six months;
5. Current criminal justice involvement with legal proceedings, which in the opinion of a medically qualified investigator indicates a risk that the patient would fail to complete the study protocol due to re-incarceration or move away from the centre's catchment area.
6. Currently taking oral or depot naltrexone therapy or enrolment in any form of naltrexone therapy within 90 days prior to study screening;
7. Any contraindication to Bup\*.

   * Participant is ineligible if they have any allergic or adverse reactions or contraindication to Buprenorphine. If participant has any allergic or adverse reaction or contraindication to Met or naloxone, or excipients of Bup-NX or Esp they can be prescribed Bup within the trial.

Primary outcomes:
measure: Count of days abstinent From illicit/non-medical opioids during weeks 2 to 24 (range: 0-161 days)
timeFrame: 24 weeks
Secondary outcomes:
measure: Clinical superiority of XR-Bup plus PSI versus Bup/Met plus PSI
timeFrame: 24 weeks
measure: Cost-effectiveness of XR-BUP versus Bup and Met
timeFrame: 24 weeks
measure: Safety of XR-Bup
timeFrame: 24 weeks
measure: Time (days) enrolled in study treatment (retention) to week 24
timeFrame: 24 weeks
measure: OUD remission status (DSM5 OUD severity; SCID-5-RV)
timeFrame: 24 weeks
measure: Clinician rating of severity, complexity and recovery strengths: ADAPT
timeFrame: 24 weeks
measure: Clinician global impression of severity and improvement): CGI-S/I;
timeFrame: 24 weeks
measure: Count of days abstinent from cocaine and illicit/non-medical benzodiazepines
timeFrame: 24 weeks
measure: Frequency of opioid (H) and cocaine (C) craving experience: CEQ-F(H) and CEQ-F(C)
timeFrame: 24 weeks
measure: Craving need and want strength for heroin and cocaine: VAS-N(H/C) and VAS-W(H/C)
timeFrame: 24 weeks
measure: Difficulties in Emotion Regulation (Short Form): DERS-SF
timeFrame: 24 weeks
measure: Depression symptoms: QIDS-SR
timeFrame: 24 weeks
measure: Work and social adjustment: WSAS
timeFrame: 24 weeks
measure: Subjective recovery and improvement: SURE
timeFrame: 24 weeks
measure: Patient rating of OUD severity and improvement:
timeFrame: 24 weeks
measure: Patient rating of OUD severity and improvement:
timeFrame: 24 weeks
measure: Alcohol consumption: typical quantity and frequency: (ALC-QFM)
timeFrame: 24 weeks
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
measure: Longer Term Outcomes
timeFrame: Through study completion, up to 4 years
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham and Solihull Mental Health NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: NHS Tayside
city: London
country: United Kingdom
facility: South London and Maudsley NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Greater Manchester Mental Health NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust
Study officials:
affiliation: South London and Maudsley NHS Foundation Trust
name: Mike Kelleher, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. 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 Aug 19;23(1):697. doi: 10.1186/s13063-022-06595-0.
citation: Marsden J, Kelleher M, Gilvarry E, Mitcheson L, Bisla J, Cape A, Cowden F, Day E, Dewhurst J, Evans R, Hardy W, Hearn A, Kelly J, Lowry N, McCusker M, Murphy C, Murray R, Myton T, Quarshie S, Vanderwaal R, Wareham A, Hughes D, Hoare Z. Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial. EClinicalMedicine. 2023 Nov 17;66:102311. doi: 10.1016/j.eclinm.2023.102311. eCollection 2023 Dec.