A Pragmatic Randomized Control Trial Comparing Models of Care in the Management of Prescription Opioid Misuse

NCT03033732 | Completed Phase 4 DMC

• 1 other identifier: CRISM 001
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 7

Brief Summary

This trial evaluates two standard of care treatments for opioid addiction: methadone and buprenorphine/naloxone. In order to improve patient care, the study will address real-world treatment conditions, including strict regulations for methadone dosing (i.e. initially dispensed daily at the pharmacy until stabilisation) vs. flexible take-home dosing for buprenorphine/naloxone. The OPTIMA study is designed with the intention to support patient-provider decision-making and evaluate health related outcomes with the overall aim of improving treatment outcomes through enhancing patient-centered approaches in clinical care.

Conditions

Opioid Use Disorder

Keywords

opioid agonist treatment; pragmatic; prescription opioid use; patient engagement

Outcome Measures

Primary Outcomes (1)

• Opioid Use

  Opioid use will be measured by the overall proportion of opioid-free urine drug screens (UDS) during the 24 weeks of the trial (excluding the assigned metabolites of opioid agonist treatments, as appropriate), with missing values defined as positive UDS (binary, laboratory assay).

  24 weeks

Secondary Outcomes (5)

• Retention in treatment

  24 weeks

• Opioid Agonist Treatment (OAT) Medication Adherence

  24 weeks

• Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs)

  24 weeks

• Patient Satisfaction

  24 weeks

• Patient Engagement

  24 weeks

Other Outcomes (4)

• Quality of life

  24 weeks

• Pain

  24 weeks

• Proportion of Participants who Initiate Taper

  24 weeks

Study Arms (2)

Methadone

OTHER

Opioid agonist treatment for opioid use disorder. Ingested in liquid oral form via strict initial daily witnessed ingestion as per local guidelines.

Drug: Methadone

Buprenorphine/Naloxone

OTHER

Opioid agonist treatment for opioid use disorder. Ingested orally via sublingual tablet form, flexible take home dosing.

Drug: Buprenorphine-Naloxone

Interventions

Methadone DRUG

Methadone is a synthetic analgesic drug used as a substitute drug in the treatment of opioid use disorder. Methadone is administered via strict daily witnessed ingestion.

Also known as: Methadose

Methadone

Buprenorphine-Naloxone DRUG

Buprenorphine/Naloxone is an opioid agonist treatment used to treat opioid use disorder. Buprenorphine/Naloxone is administered via flexible take home dosing once the patient has reached stabilization as per physician discretion.

Also known as: Suboxone

Buprenorphine/Naloxone

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be aged between 18 and 64 years of age inclusively;
• Prescription opioid use disorder (as defined by the Diagnostic and Statistical Manual of Mental Disorders-5 criteria), which requires opioid agonist therapy as per the discretion of the physician;
• Female participants may be eligible if:
• Is of non-childbearing potential, defined as (i) post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age); or (ii) documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy).
• Is of childbearing potential, has a negative pregnancy test at screening and and agrees to use an acceptable method of birth control throughout study;
• Be willing to be randomized to 24 weeks of either methadone or buprenorphine/naloxone adapted model of care, and to be followed for the duration of the trial;
• Be able to provide written informed consent;
• Be willing to comply with study procedures;
• Be able to communicate in English or French.

You may not qualify if:

• Any disabling medical condition as assessed by medical history, physical exam, vital signs and/or laboratory assessments that, in the opinion of the study physician, precludes the safe participation in the study or the ability to provide fully informed consent;
• Any disabling, unstable or acute mental condition that in the opinion of the study physician precludes safe participation in the study or ability to provide fully informed consent;
• Heroin reported as the most frequently used opioid in the past 30 days;
• Taken methadone or buprenorphine/naloxone for Opioid Use Disorder maintenance treatment in the four weeks prior to screening;
• Pain of sufficient severity as to require ongoing pain management with opioids;
• History of a severe adverse event, hypersensitivity reaction, or allergic reaction to either methadone or buprenorphine/naloxone;
• Pregnant, nursing, or planning to become pregnant during the study period;
• Currently taking or have taken an investigational drug in another study in the last 30 days, confirmed via self-report;
• Pending legal action or other reasons in the opinion of the study physician that might prevent completion of the study;
• Presence of a substance use disorder that, in the opinion of the study physician, precludes safe participation in the study (e.g. unstable or severe alcohol use disorder, unstable or severe benzodiazepine use disorder);
• Current treatment with medications that may interact with either methadone or buprenorphine/naloxone (e.g. Clonazepam, Benzodiazepines) OR anticipation that the patient may need to initiate such treatment during the trial that is deemed unsafe by the study physician or could prevent study completion;

Sponsors & Collaborators

• Didier Jutras Aswad: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (7)

Calgary Opioid Dependency Program

Calgary, Alberta, T2R 0X7, Canada

Location

Edmonton Opioid Dependency Program

Edmonton, Alberta, T5J 0G5, Canada

Location

Rapid Access Addictions Clinic-St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Ontario Addiction Treatment Centres- Sudbury Clinic

Greater Sudbury, Ontario, P3C 5K8, Canada

Location

Addiction Medicine Service- Centre for Addictions and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Centre de Recherche du CHUM

Montreal, Quebec, H2X 0A9, Canada

Location

Centre de Recherche et d'Aide pour Narcomane

Montreal, Quebec, H2X 1S7, Canada

Location

Related Publications (11)

• Bastien G, Abboud A, McAnulty C, Mahroug A, Le Foll B, Socias ME, Juteau LC, Dubreucq S, Jutras-Aswad D. Concordance Between Urine Drug Screening and Self-Reported Use in the Context of a Pragmatic Randomized-Controlled Trial in People with Prescription-Type Opioid Use Disorder: Concordance entre le depistage de drogues dans l'urine et l'usage autodeclare dans le contexte d'un essai pragmatique controle a repartition aleatoire chez des personnes presentant un trouble lie a l'usage d'opioides vendus sur ordonnance. Can J Psychiatry. 2026 Jan;71(1):41-52. doi: 10.1177/07067437251367180. Epub 2025 Aug 28.

  PMID: 40874578 DERIVED

• Bouthillier A, Bastien G, McAnulty C, Bakouni H, Le Foll B, Socias ME, Jutras-Aswad D. Opioid consumption frequency and its associations with potential life problems during opioid agonist treatment in individuals with prescription-type opioid use disorder: exploratory results from the OPTIMA Study. Harm Reduct J. 2025 Feb 8;22(1):14. doi: 10.1186/s12954-025-01157-4.

  PMID: 39923043 DERIVED

• Langlois J, Fairbairn N, Jutras-Aswad D, Le Foll B, Lim R, Socias ME. Characterising methamphetamine/amphetamine use among opioid agonist therapy-seeking adults with prescription-type opioid use disorder in Canada. Drug Alcohol Rev. 2024 Nov;43(7):1905-1912. doi: 10.1111/dar.13863. Epub 2024 May 9.

  PMID: 38721650 DERIVED

• Bastien G, Abboud A, McAnulty C, Elkrief L, Ledjiar O, Socias ME, Le Foll B, Bahji A, Brissette S, Marsan S, Jutras-Aswad D. Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial. J Dual Diagn. 2024 Jul-Sep;20(3):189-200. doi: 10.1080/15504263.2024.2329267. Epub 2024 Apr 5.

  PMID: 38580298 DERIVED

• Socias ME, Cui Z, Le Foll B, Lei J, Stewart S, Anand R, Jutras-Aswad D. Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial. HIV Med. 2024 Jul;25(7):817-825. doi: 10.1111/hiv.13636. Epub 2024 Mar 20.

  PMID: 38506171 DERIVED

• Bahji A, Bastien G, Bach P, Choi J, Le Foll B, Lim R, Jutras-Aswad D, Socias ME. The Association Between Self-Reported Anxiety and Retention in Opioid Agonist Therapy: Findings From a Canadian Pragmatic Trial. Can J Psychiatry. 2024 Mar;69(3):172-182. doi: 10.1177/07067437231194385. Epub 2023 Sep 12.

  PMID: 37697811 DERIVED

• Elkrief L, Bastien G, McAnulty C, Bakouni H, Hebert FO, Socias ME, Le Foll B, Lim R, Ledjiar O, Marsan S, Brissette S, Jutras-Aswad D; OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse. Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study. J Subst Use Addict Treat. 2023 Jun;149:209031. doi: 10.1016/j.josat.2023.209031. Epub 2023 Mar 30.

  PMID: 37003540 DERIVED

• Bastien G, McAnulty C, Ledjiar O, Socias ME, Le Foll B, Lim R, Hassan AN, Brissette S, Marsan S, Talbot A, Jutras-Aswad D; OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse. Effects of Buprenorphine/Naloxone and Methadone on Depressive Symptoms in People with Prescription Opioid Use Disorder: A Pragmatic Randomised Controlled Trial. Can J Psychiatry. 2023 Aug;68(8):572-585. doi: 10.1177/07067437221145013. Epub 2022 Dec 14.

  PMID: 36519188 DERIVED

• McAnulty C, Bastien G, Eugenia Socias M, Bruneau J, Le Foll B, Lim R, Brissette S, Ledjiar O, Marsan S, Talbot A, Jutras-Aswad D; OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse. Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial. Drug Alcohol Depend. 2022 Oct 1;239:109604. doi: 10.1016/j.drugalcdep.2022.109604. Epub 2022 Aug 17.

  PMID: 36037586 DERIVED

• Jutras-Aswad D, Le Foll B, Ahamad K, Lim R, Bruneau J, Fischer B, Rehm J, Wild TC, Wood E, Brissette S, Gagnon L, Fikowski J, Ledjiar O, Masse B, Socias ME; OPTIMA Research Group within the Canadian Research Initiative in Substance Misuse. Flexible Buprenorphine/Naloxone Model of Care for Reducing Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: An Open-Label, Pragmatic, Noninferiority Randomized Controlled Trial. Am J Psychiatry. 2022 Oct;179(10):726-739. doi: 10.1176/appi.ajp.21090964. Epub 2022 Jun 15.

  PMID: 35702828 DERIVED

• Socias ME, Ahamad K, Le Foll B, Lim R, Bruneau J, Fischer B, Wild TC, Wood E, Jutras-Aswad D. The OPTIMA study, buprenorphine/naloxone and methadone models of care for the treatment of prescription opioid use disorder: Study design and rationale. Contemp Clin Trials. 2018 Jun;69:21-27. doi: 10.1016/j.cct.2018.04.001. Epub 2018 Apr 5.

  PMID: 29627621 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders; Patient Participation

Interventions

Methadone; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Didier Jutras Aswad, MD

  Canadian Research Initiative in Substance Misuse

  PRINCIPAL INVESTIGATOR

• Maria E Socias, MD

  British Columbia Centre on Substance Use

  PRINCIPAL INVESTIGATOR

• Keith Ahamad, MD

  British Columbia Centre on Substance use

  PRINCIPAL INVESTIGATOR

• Bernard LeFoll, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

• Ron Lim, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Julie Bruneau, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

• Evan Wood, MD

  British Columbia Centre on Substance Use

  PRINCIPAL INVESTIGATOR

• Cameron Wild, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Jurgen Rehm, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Didier Jutras Aswad - Principal Investigator

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: January 27, 2017
• Study Start: October 2, 2017
• Primary Completion: March 31, 2020
• Study Completion: December 31, 2020
• Last Updated: June 16, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)