Office-based Methadone Versus Buprenorphine to Address Retention in Medication for Opioid Use Disorder Treatment.

Office-based Methadone Versus Buprenorphine to Address Retention in Medication for Opioid Use Disorder Treatment - A Pragmatic Hybrid Effectiveness/Implementation Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Methadone; Drug: Buprenorphine (BUP)

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.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jessica Research Associate; Phone Number: 203-785-6821; Email: j.mckenzie@yale.edu
• Study Contact Backup: Name: Melissa Gordon; Phone Number: 7415 203-937-3486; Email: melissa.gordon@yale.edu

Study Locations

• United States
  • California
    • Oakland, California, United States, 94602
      • Recruiting
      • Highland Hospital Bridge Clinic at Alameda Health System
      • Principal Investigator: Monish Ullal, MD
      • Contact: Jhoselyn Pineda; Phone Number: (510)214-3649; Email: emboss.ctn0131@gmail.com
    • San Francisco, California, United States, 94103
      • Recruiting
      • Outpatient Buprenorphine Induction Clinic, University of California, San Francisco
      • Principal Investigator: Paula Lum, MD
      • Principal Investigator: Andy Tompkins, MD
      • Sub-Investigator: Christine Soran, MD
      • Contact: Kristina Toma; Phone Number: 415-254-0398; Email: EMBOSS@ucsf.edu
  • Colorado
    • Denver, Colorado, United States, 80205
      • Recruiting
      • Rapid Start Clinic, Kaiser Permanente Colorado
      • Principal Investigator: Ingrid Binswanger, MD
      • Contact: Jennifer Barrow; Phone Number: (303)-739-3666; Email: EMBOSS@kp.org
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Officed Based Addiction Treatment Program, Boston Medical Center
      • Principal Investigator: Zoe Weinstein, MD
      • Contact: Emily Oot; Phone Number: 857-283-7620; Email: EMBOSS@bmc.org
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Recruiting
      • Hennepin Healthcare Addiction Medicine
      • Principal Investigator: Gavin Bart, MD
      • Contact: Fiona Giles; Phone Number: (763) 568-2785; Email: EMBOSSstudy@bermancenter.org
  • West Virginia
    • Huntington, West Virginia, United States, 25703
      • Recruiting
      • Marshall University Division of Addiction Sciences P.R.O.A.C.T
      • Principal Investigator: Zachary Hansen, MD
      • Sub-Investigator: Todd Davies, PhD
      • Contact: Brynn M Taylor; Phone Number: 740-302-0845; Email: taylor975@marshall.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: Office-based methadone; Under special Drug Enforcement Administration (DEA) exception, Clinician prescribes methadone and oral methadone is administered and/or dispensed at a pharmacy which also has an exception to do so. All randomized controlled trial (RCT) participants are offered additional behavioral treatments (e.g., individual, group, telehealth, phone-based).	Drug: Methadone; Drug: Methadone Possible formulations: 10 and 50 mg tablets
Active Comparator: Office-based buprenorphine (BUP); Clinician prescribes BUP formulations that are dispensed at a pharmacy or administered in the office (e.g., extended-release formulations). All RCT participants are offered additional behavioral treatments (e.g., individual, group, telehealth, phone-based).	Drug: Buprenorphine (BUP); 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),

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of continuous treatment with site clinician-prescribed methadone or buprenorphine, as randomized, during the 168 days post-randomization among RCT participants.	This measure is based on PDMP data for methadone and non-injectable buprenorphine and EMR data for injectable buprenorphine formulations	up to Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant satisfaction with MOUD	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.	up to Day 168
Total number of self-reported overdose events per total number of participant days at risk.	The Overdose Calendar Recall instrument collects overdose events.	up to Day 168
Number of self-reported continuous treatment days in any FDA-approved formulation of MOUD treatment during the 168 days post-randomization.	This measure is assessed using the MOUD Calendar Based Recall Recall Instruments.	up to Day 168
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.	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.	up to Day 168
Total number of days receiving any FDA-approved MOUD formulation during the 168 days post-randomization.	This measure is assessed using EMR (for injectable MOUD formulations) and PDMP data.	up to Day 168
The longest duration of continuous treatment episode with MOUD, as randomized, during the 168 days post randomization.	This measure is based on PDMP and/or EMR data.	up to Day 168
Total number of days receiving methadone or buprenorphine, during the 168 days post-randomization.	This measure is assessed using EMR (for injectable MOUD formulations) and PDMP data.	up to Day 168
Total number of days of self-reported non-prescribed opioid use during each 28-day assessment period.	This measure is assessed by the Opioid Use Calendar Based Recall instruments.	up to Day 168
Total number of days of self-reported non-prescribed stimulant use during each 28-day assessment period.	This measure is assessed by the Timeline Followback instrument.	up to Day 168
Total number of days of self-reported non-prescribed benzodiazepine use during each 28-day assessment period.	This measure is assessed by the Timeline Followback instrument.	up to Day 168
Urine toxicology	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.	up to Day 168
Total number of self-reported injection drug use related events during each 28-day assessment period.	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.	Up to Day 168
Mean score Pain measured using Pain, Enjoyment of Life and General Activity (PEG) Scale (PEG-3)	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.	Up to Day 168
Total number of self-reported days with acute care utilization (ED or hospitalization) during each 28-day assessment period.	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.	Up to Day 168
Total number of behavioral counseling service visits attended per participant during each 28-day assessment period.	Assessed by EMR extraction and the Health Services Utilization.	Up to Day 168
Total number of planned prescriber visits attended during each 28-day assessment period.	Assessed by EMR extraction.	Up to Day 168
Pharmacist practice fidelity	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.	Up to Day 168

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention in office-based methadone treatment	Retention will be defined as the number of days of continuous office-based methadone treatment (time to event outcome) staring at day 168. Discontinuation of methadone for the extended study component will be defined as more than a self-reported 30-day gap in receipt of methadone or non-response on two consecutive 60-day assessments. The date of discontinuation will be the end of the last 30-day period with any self-reported office-based methadone treatment. Participants who remain in continuous treatment through the end of the study and will be censored on day of the last 60 day assessment. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Percentage of days covered of self-reported pharmacy dispensed methadone treatment	Percentage of days covered of self-reported pharmacy dispensed methadone treatment (i.e., number of self-reported days covered per total days observed). Only collected in extended study participants.	starting at day 168 post enrollment up to 2 years
Total number of self-reported overdose events	To assess overdose events, participants will self-report the number of overdose events in the past 28 days. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Methadone dose	Participants will self-report the most recent daily dose (in milligrams) of methadone prescribed and obtained from the pharmacy. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Days of treatment	Days of treatment will be the count of self-reported number of days the participant self reported taking prescribed methadone. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Treatment Effectiveness Assessment (TEA)	The TEA collects self-report data across four domains: substance use, health, lifestyle, and community. This will be analyzed as a repeated measure of overall numerical score. Total score range 4-40. higher scores mean greater improvement. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Health service utilization	Participants will be asked to report the inpatient and outpatient services they used in the past 28 days. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Health related quality of life	To assess health related quality of life, participants will self-report their general health, physical health, and mental health during the past 28 days. This will be analyzed as a repeated measure of overall numerical score. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Crime and criminal justice involvement	To assess crime and criminal justice, participants will self-report how many days in the past 60 days they have been incarcerated, if they have been in contact with the court, criminal justice system, or probation/parole officer and how many of those days in the past 60 they were incarcerated, in contact with the court, criminal justice system or probation/parole officer. Criminal justice involvement will be defined as the percentage of days of self-reported involvement (i.e., number of self-reported days per total days observed). Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
End of study status	End of study status for participants which includes; office-based methadone treatment at end of study, withdrew consent, deceased, unable to contact, no longer being prescribed methadone from the site. End of study status will be reported by study site Research Associates or Site Clinicians. Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years
Substance use	To assess substance use, participants will self-report how many of the past 60 days that they used a substance. Monthly substance use obtained through survey assessment at each 60- day assessment. Total number of days of self-reported substance use during each 60 day assessment period (discrete or continuous outcome, repeated measure). Only collected in extended study participants.	Starting at day 168 post enrollment up to 2years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH); University of California, San Francisco; Kaiser Permanente; The Emmes Company, LLC; Hennepin Healthcare Research Institute; Alameda Health System; Boston Medical Center (BMC); Marshall Health
• Investigators: Principal Investigator: David Fiellin, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Opioid Use Disorder; Methadone; Buprenorphine
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Ketones; Buprenorphine; Methadone
• Other Study ID Numbers: 2000033271; CTN-0131 (Other Identifier: Clinical Trials Network); 5UG1DA015831-21 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The National Institute on Drug Abuse (NIDA) Data Share web site is an electronic environment that allows data from completed clinical trials to be distributed to investigators and the public in order to promote new research, encourage further analyses, and disseminate information to the community. Secondary analyses produced from data sharing multiply the scientific contribution of the original research. NIH expects and supports the timely release and sharing of final research data from NIH-supported studies for use by other researchers to expedite the translation of research results into knowledge, products and procedures to improve human health.
• IPD Sharing Time Frame: Data sets will be available after (1) the primary paper has been accepted for publication, or (2) the data is locked for more than 18 months, whichever comes first.
• IPD Sharing Access Criteria: Public
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No