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

NCT ID: NCT03033732

Last Updated: 2021-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-02
• Study Completion Date: 2020-12-31

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.

Detailed Description

This is a multicenter, open-label, 2-arm, randomized trial with a pragmatic design involving 276 individuals with prescription opioid use disorder. Participants will be randomized to receive either:

1. Methadone provided via initial daily witnessed ingestion as per local guidelines.

2. Buprenorphine/naloxone maintenance therapy provided via flexible take-home dose regimens dispensed as per the physician's discretion, once clinical stability is achieved.

Once randomized to a study medication and treatment initiation and induction has begun, study physicians and participants will discuss the treatment plans and procedures going forward. Once treatment initiation has taken place, the participant will attend study visits every 2 weeks (including collection of urine samples) for the 24-week intervention period. For all study sites, standardized guidelines exist and will be adhered to for the safe induction of both medications. Frequency of illicit opioid use, intensity of craving and other secondary endpoints will also be assessed via standardized questionnaires.

Conditions

Opioid Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Methadone

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

Group Type: OTHER

Methadone

Intervention Type: 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.

Buprenorphine/Naloxone

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

Group Type: OTHER

Buprenorphine-Naloxone

Intervention Type: 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.

Interventions

Methadone

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.

Intervention Type: DRUG

Buprenorphine-Naloxone

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.

Intervention Type: DRUG

Other Intervention Names

Methadose; Suboxone

Eligibility Criteria

Inclusion Criteria

1. Be aged between 18 and 64 years of age inclusively;

2. 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;

3. Female participants may be eligible if:

1. 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).

2. Is of childbearing potential, has a negative pregnancy test at screening and and agrees to use an acceptable method of birth control throughout study;

4. 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;

5. Be able to provide written informed consent;

6. Be willing to comply with study procedures;

7. Be able to communicate in English or French.

Exclusion Criteria

1. 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;

2. 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;

3. Heroin reported as the most frequently used opioid in the past 30 days;

4. Taken methadone or buprenorphine/naloxone for Opioid Use Disorder maintenance treatment in the four weeks prior to screening;

5. Pain of sufficient severity as to require ongoing pain management with opioids;

6. History of a severe adverse event, hypersensitivity reaction, or allergic reaction to either methadone or buprenorphine/naloxone;

7. Pregnant, nursing, or planning to become pregnant during the study period;

8. Currently taking or have taken an investigational drug in another study in the last 30 days, confirmed via self-report;

9. Pending legal action or other reasons in the opinion of the study physician that might prevent completion of the study;

10. 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);

11. 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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Didier Jutras Aswad

OTHER

Sponsor Role: lead

Responsible Party

Didier Jutras Aswad

Dr. Didier Jutras Aswad - Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Didier Jutras Aswad, MD

Role: PRINCIPAL_INVESTIGATOR

Canadian Research Initiative in Substance Misuse

Maria E Socias, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Centre on Substance Use

Keith Ahamad, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Centre on Substance use

Bernard LeFoll, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Ron Lim, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Julie Bruneau, MD

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Evan Wood, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Centre on Substance Use

Cameron Wild, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Jurgen Rehm, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Calgary Opioid Dependency Program

Calgary, Alberta, Canada

Edmonton Opioid Dependency Program

Edmonton, Alberta, Canada

Rapid Access Addictions Clinic-St. Paul's Hospital

Vancouver, British Columbia, Canada

Ontario Addiction Treatment Centres- Sudbury Clinic

Greater Sudbury, Ontario, Canada

Addiction Medicine Service- Centre for Addictions and Mental Health

Toronto, Ontario, Canada

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Centre de Recherche et d'Aide pour Narcomane

Montreal, Quebec, Canada

Countries

Canada

References

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. 2025 Aug 28:7067437251367180. doi: 10.1177/07067437251367180. Online ahead of print.

Reference Type: DERIVED

PMID: 40874578 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39923043 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38721650 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38580298 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38506171 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37697811 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37003540 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36519188 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36037586 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35702828 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29627621 (View on PubMed)

Other Identifiers

CRISM 001

Identifier Type: -

Identifier Source: org_study_id