Opioid Use Disorder
Conditions
Keywords
Opioid Use Disorder, Methadone, Buprenorphine
Brief summary
The purpose of this clinical trial is to compare the effectiveness of office-based methadone with pharmacy administration and/or dispensing to office-based buprenorphine for the treatment of opioid use disorder. This study will also examine factors influencing the implementation of office-based methadone.
Detailed description
This study is a randomized, pragmatic hybrid type 1 effectiveness/implementation multisite (approximately 6 sites) trial to determine whether office-based methadone with pharmacy administration and/or dispensing or buprenorphine (BUP) results in greater treatment retention in approximately 600 patients with opioid use disorder (OUD). This trial will also identify implementation barriers, facilitators and acceptability at the patient, provider and health-systems level for office-based methadone with pharmacy administration and/or dispensing. An ancillary extended study was added to this trial in January of 2026. A sub-set of current participants that were receiving office based methadone as of day 168 of the parent study will continue to be followed for other pre-specified outcomes.
Interventions
DRUGMethadone
Drug: Methadone Possible formulations: 10 and 50 mg tablets
Drug: Buprenorphine (BUP) Possible formulations: A. Buprenorphine, 225 mcg to 24 mg, 225 mcg to 32 mg per day, B. Buprenorphine (Extended release), 300 mg q 28 days (Sublocade), 100 mg q 28 days (Sublocade), 8 mg q 7 days (Brixadi), 16 mg q 7 days (Brixadi), 24 mg q 7 days (Brixadi), 32 mg q 7 days (Brixadi), 64 mg q 28 days (Brixadi), 96 mg q 28 days (Brixadi), 128 mg q 28 days (Brixadi),
Sponsors
Yale University
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
The Emmes Company, LLC
University of California, San Francisco
Boston Medical Center (BMC)
Hennepin Healthcare Research Institute
Alameda Health System
Marshall Health
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The comparative effectiveness of two strategies to address retention in medication for opioid use disorder (MOUD) treatment will be tested over a 168-day period. Behavioral treatments offered to patients are designed to be similar across the two medication conditions. Office-based methadone where the clinician prescribes methadone and oral methadone is administered and/or dispensed at a pharmacy. Providers and Randomized Control Trial (RCT) participants will have flexibility to use behavioral and pharmacological services as clinically indicated. Office-based buprenorphine (BUP) where the clinician prescribes BUP formulations that are dispensed at a pharmacy or administered in the office (e.g., extended-release formulations). Providers and RCT participants will have flexibility to use behavioral and pharmacological services as clinically indicated.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older; * Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD; * Are initiating a new MOUD treatment episode
Exclusion criteria
* Have been prescribed (and ingested) or been administered more than 72 hours of MOUD in the 7 days prior to randomization as a "bridge" to the new OUD treatment episode. Such MOUD may include prescribed (and ingested) or administered medically managed withdrawal (aka detoxification). * Known contraindication to methadone or BUP * Unwilling to pursue or continue pre-natal care or pregnancy counseling if determined pregnant by urine human chorionic gonadotropin (hCG) testing at the screening assessment * Be actively suicidal or severely cognitively impaired (e.g., dementia, untreated psychosis) precluding informed consent as determined by site clinician * Current severe comorbid substance use disorder requiring residential or inpatient treatment services as determined by site clinician * Be unable to provide locator information including one or more contacts in addition to themselves * Be unwilling to follow study procedures (e.g., unwilling to receive treatment from site clinician, use the study pharmacy, unwilling to be randomized to BUP or methadone, or will be unavailable for the follow-up assessments) including allowing the researchers to access their record in the EMR and state's prescription drug monitoring program * Have previously enrolled in CTN-0131 * Currently enrolled in another research study which will conflict with study procedures * Are currently in jail, prison or other overnight facility as required by a court of law or have pending legal action that could prevent participation in study activities * Unable to conduct research assessments in English as determined by Site PI or their designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of days of continuous treatment with site clinician-prescribed methadone or buprenorphine, as randomized, during the 168 days post-randomization among RCT participants. | up to Day 168 | This measure is based on PDMP data for methadone and non-injectable buprenorphine and EMR data for injectable buprenorphine formulations |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of self-reported continuous treatment days in any FDA-approved formulation of MOUD treatment during the 168 days post-randomization. | up to Day 168 | This measure is assessed using the MOUD Calendar Based Recall Recall Instruments. |
| Number of self-reported continuous treatment days in formal OUD treatment, according to American Society of Addiction Medicine (ASAM) levels of care 1-4, during the 168 days post-randomization. | up to Day 168 | This measure is assessed using one or more of the following: The Health Services Utilization instrument, a brief structured interview regarding health care utilization (inpatient and outpatient) collecting information on the type and amount of services received, Timeline Followback Medications, MOUD Calendar Based Recall, and Treatment Dates instruments. |
| Total number of days receiving any FDA-approved MOUD formulation during the 168 days post-randomization. | up to Day 168 | This measure is assessed using EMR (for injectable MOUD formulations) and PDMP data. |
| The longest duration of continuous treatment episode with MOUD, as randomized, during the 168 days post randomization. | up to Day 168 | This measure is based on PDMP and/or EMR data. |
| Total number of days receiving methadone or buprenorphine, during the 168 days post-randomization. | up to Day 168 | This measure is assessed using EMR (for injectable MOUD formulations) and PDMP data. |
| Total number of days of self-reported non-prescribed opioid use during each 28-day assessment period. | up to Day 168 | This measure is assessed by the Opioid Use Calendar Based Recall instruments. |
| Total number of days of self-reported non-prescribed stimulant use during each 28-day assessment period. | up to Day 168 | This measure is assessed by the Timeline Followback instrument. |
| Total number of days of self-reported non-prescribed benzodiazepine use during each 28-day assessment period. | up to Day 168 | This measure is assessed by the Timeline Followback instrument. |
| Urine toxicology | up to Day 168 | Total number of monthly (28 days) urines negative for non-prescribed opioids during the 168 days post-randomization. Non-prescribed opioids will be determined using the Opioid Use Calendar Based Recall instrument. |
| Participant satisfaction with MOUD | up to Day 168 | Proportion of RCT participants who report at the assessment scheduled to be collected on day 28 that the medication they received was at least "Somewhat helpful" on the Satisfaction with MOUD Provider Scale instrument. |
| Total number of self-reported overdose events per total number of participant days at risk. | up to Day 168 | The Overdose Calendar Recall instrument collects overdose events. |
| Total number of self-reported injection drug use related events during each 28-day assessment period. | Up to Day 168 | Assessment of Infectious or Other Complications of Injection Drug Use assess for skin abscesses, ulcers , cellulitis, osteoarticular septic arthritis, osteomyelitis, epidural infection , endovascular, new injection-related viral infections diagnosis of Hepatitis or HIV. |
| Mean score Pain measured using Pain, Enjoyment of Life and General Activity (PEG) Scale (PEG-3) | Up to Day 168 | Mean scores on the PEG-3 instrument over time. The PEG-3 instrument is collected every 28 days. The mean score is the average of the three 0-10 rated items. Total score range 0-10. Higher scores indicate worse pain. |
| Total number of self-reported days with acute care utilization (ED or hospitalization) during each 28-day assessment period. | Up to Day 168 | The Health Services Utilization instrument is a brief, structured interview regarding health care utilization (inpatient and outpatient) collecting information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment) and self-help sources of support (e.g., NA). Also assessed are receipt of formal and informal addiction and mental health treatment services RCT participants might have received outside the study interventions. |
| Total number of behavioral counseling service visits attended per participant during each 28-day assessment period. | Up to Day 168 | Assessed by EMR extraction and the Health Services Utilization. |
| Total number of planned prescriber visits attended during each 28-day assessment period. | Up to Day 168 | Assessed by EMR extraction. |
| Pharmacist practice fidelity | Up to Day 168 | Assessed by MOUD Visit Checklist completion over time. The MOUD Visit Checklist collects clinical activities that might be performed by a pharmacist at each pharmacy, such as performing medication reconciliation; conducting safety assessments, adverse effects of methadone, recent overdose events, checking the patient's controlled medications prescription status using the PDMP before dispensing methadone; providing patient education/counseling; communicating with the clinician regarding any concern; and administering one methadone dose at the pharmacy and/or dispensing methadone according to the prescription. |
Countries
United States
Contacts
CONTACTJessica Research Associate
CONTACTMelissa Gordon
PRINCIPAL_INVESTIGATORDavid Fiellin, MD
Yale University
Outcome results
None listed