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

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

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.

Study Overview

• Status: Completed
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Methadone; Drug: Buprenorphine-Naloxone

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.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Calgary Opioid Dependency Program
    • Edmonton, Alberta, Canada, T5J 0G5
      • Edmonton Opioid Dependency Program
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Rapid Access Addictions Clinic-St. Paul's Hospital
  • Ontario
    • Sudbury, Ontario, Canada, P3C 5K8
      • Ontario Addiction Treatment Centres- Sudbury Clinic
    • Toronto, Ontario, Canada, M6J 1H4
      • Addiction Medicine Service- Centre for Addictions and Mental Health
  • Quebec
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du CHUM
    • Montréal, Quebec, Canada, H2X 1S7
      • Centre de Recherche et d'Aide pour Narcomane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Quality of Life (QoL) will be evaluated via the EQ5-D self-report questionnaires administered at Treatment Initiation and every 4 weeks.	24 weeks
Pain	Pain will be assessed via Brief Pain Inventory self-report questionnaire at Screening to determine eligibility, Treatment Initiation and every 4 weeks for the 24 week intervention period.	24 weeks
Proportion of Participants who Initiate Taper	The proportion of patients who initiate taper will be assessed by using a standardized induction case report form completed via both pharmacy abstraction and self-report. The pharmacy record abstraction will collect information on opioid agonist treatment use and on the days between follow up visits, as well as information on end or switching of opioid agonist treatments, missing doses and reason any change in medication status or dose change. The participant will also be asked about his/her use of opioid agonist treatments in the past 2 weeks or since the last study visit collecting information similar to that information collected in the pharmacy abstraction.	24 weeks
Cost-effectiveness	Information on health service utilization will be collected at baseline and every 4 weeks for the 24-week intervention period. Items were selected from modules selected from the European Addiction Severity Index which collect self-report data on income, medical/medication status, healthcare provider visits, and criminal activity. This information will either be collected on paper source or entered by the participant directly into the Electronic Data Capture (EDC) system.	24 weeks

Collaborators and Investigators

• Sponsor: Didier Jutras Aswad
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: 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

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2017
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: January 26, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): June 16, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: patient engagement; pragmatic; opioid agonist treatment; prescription opioid use
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Respiratory System Agents; Antitussive Agents; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination; Methadone
• Other Study ID Numbers: CRISM 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No