Clinical trial NCT03033732: A Pragmatic Randomized Control Trial Comparing Models of Care in the Management of Prescription Opioid Misuse
Official title: Optimizing Patient Centered-Care: A Pragmatic Randomized Control Trial Comparing Models of Care in the Management of Prescription Opioid Misuse (OPTIMA Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Opioid Use Disorder
Keywords: opioid agonist treatment
pragmatic
prescription opioid use
patient engagement
Lead sponsor: Canadian Research Initiative in Substance Misuse
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-01-27
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Opioid Use
timeFrame: 24 weeks
Secondary outcomes:
measure: Retention in treatment
timeFrame: 24 weeks
measure: Opioid Agonist Treatment (OAT) Medication Adherence
timeFrame: 24 weeks
measure: Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 weeks
measure: Patient Satisfaction
timeFrame: 24 weeks
measure: Patient Engagement
timeFrame: 24 weeks
Other outcomes:
measure: Quality of life
timeFrame: 24 weeks
measure: Pain
timeFrame: 24 weeks
measure: Proportion of Participants who Initiate Taper
timeFrame: 24 weeks
measure: Cost-effectiveness
timeFrame: 24 weeks
Locations:
city: Calgary
country: Canada
facility: Calgary Opioid Dependency Program
state: Alberta
city: Edmonton
country: Canada
facility: Edmonton Opioid Dependency Program
state: Alberta
city: Vancouver
country: Canada
facility: Rapid Access Addictions Clinic-St. Paul's Hospital
state: British Columbia
city: Sudbury
country: Canada
facility: Ontario Addiction Treatment Centres- Sudbury Clinic
state: Ontario
city: Toronto
country: Canada
facility: Addiction Medicine Service- Centre for Addictions and Mental Health
state: Ontario
city: Montréal
country: Canada
facility: Centre de Recherche du CHUM
state: Quebec
city: Montréal
country: Canada
facility: Centre de Recherche et d'Aide pour Narcomane
state: Quebec
Study officials:
affiliation: Canadian Research Initiative in Substance Misuse
name: Didier Jutras Aswad, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Centre on Substance Use
name: Maria E Socias, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Centre on Substance use
name: Keith Ahamad, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Addiction and Mental Health
name: Bernard LeFoll, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Ron Lim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Julie Bruneau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Centre on Substance Use
name: Evan Wood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Cameron Wild, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Addiction and Mental Health
name: Jurgen Rehm, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.