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

Study Overview
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Brief Summary
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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
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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: Methadone provided via initial daily witnessed ingestion as per local guidelines. 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.

Official Title
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Optimizing Patient Centered-Care: A Pragmatic Randomized Control Trial Comparing Models of Care in the Management of Prescription Opioid Misuse (OPTIMA Trial)

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Methadone
* Drug: Buprenorphine-Naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Methadone<br>Opioid agonist treatment for opioid use disorder. Ingested in liquid oral form via strict initial daily witnessed ingestion as per local guidelines. | Drug: Methadone<br>* 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.<br>* Other names: Methadose;|
| Other: Buprenorphine/Naloxone<br>Opioid agonist treatment for opioid use disorder. Ingested orally via sublingual tablet form, flexible take home dosing. | Drug: Buprenorphine-Naloxone<br>* 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.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention in treatment | Retention in treatment is defined as the proportion of participants on assigned opioid agonist treatment (OAT) at the end of the study, as defined by having both a) an active prescription for the assigned OAT at week 24, and b) a positive UDS result for the assigned OAT at week 24. | 24 weeks | 
| Opioid Agonist Treatment (OAT) Medication Adherence | OAT medication adherence is defined as the proportion of assigned treatment doses received over the 24-week trial period assessed by both Pharmacy Abstraction and participant self-report. | 24 weeks | 
| Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs) | Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs) throughout the duration of the trial. Adverse events and SAEs will be collected during study visits by means of open questions (e.g., has there been any changes to your health since the last study visit?). Also, the observation of clinically significant change in lab test results, fatal or non-fatal overdoses, and precipitated withdrawal symptoms from buprenorphine/naloxone inductions will be used to document AEs and SAEs. All AEs and SAEs will be documented using an AE Log in which the date and time of onset, the end date and time (i.e., when the AE was resolved or stabilized), the severity of the event, any action taken with respect to the study medication (e.g., no treatment or dose adjustment), and the relationship with study protocol or study medication will be recorded. | 24 weeks | 
| Patient Satisfaction | Patient satisfaction to the assigned treatment will be recorded on the Client Satisfaction Questionnaire (CSQ-8) and will be administered at 4, 12, and 24 weeks (end of study). | 24 weeks | 
| Patient Engagement | Patient engagement in treatment will be measured through self-report questionnaires administered at Treatment Initiation, week 4, week 12, and week 24 visits. The primary measure of ongoing patient engagement will be administered at Treatment Initiation and every 2 weeks. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid agonist treatment, pragmatic, prescription opioid use, patient engagement