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

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.

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.

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;