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: Not yet 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.

• 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

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 or unwilling to provide reliable locator information including 2 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 40 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 7 28 days (Brixadi) 96 mg q 7 28 days (Brixadi) 128 mg q 7 28 days (Brixadi)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of continuous treatment with study site clinician-prescribed methadone or buprenorphine, as randomized, during the 168 days post-randomization among RCT participants.	MOUD dispensed to the participant including medication, duration of prescription and daily dose prescribed data will be extracted from the state prescription drug monitoring program (PDMP) or the electronic medical record (EMR).	up to Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of self-reported days in any FDA-approved formulation of MOUD treatment (e.g., buprenorphine, methadone or naltrexone) during the 168 days post-randomization.	The MOUD Calendar Based Recall (Self-Report) form is used to collect self-reported prescribed medications for OUD.	up to Day 168
Number of self-reported 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 information will be obtained from one or more of the following: 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
Number of days prescribed any FDA-approved MOUD formulation during the 168 days post-randomization.	MOUD dispensed to the participant including medication, duration of prescription and daily dose prescribed data will be extracted from the state prescription drug monitoring program (PDMP) or the electronic medical record (EMR).	up to Day 168
Number of days of self-reported non-prescribed opioid use per month.	The Opioid Use Calendar Based Recall instrument is used to collect self-reported non-prescribed opioid use.	up to Day 168
Number of days of self-reported non-prescribed stimulant use per month.	The Timeline Followback instrument collects self-reported drug and alcohol use.	up to Day 168
Number of days of self-reported non-prescribed benzodiazepine use per month.	The Timeline Followback instrument collects self-reported drug and alcohol use.	up to Day 168
Urine toxicology	Number of monthly 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 self-report.	up to Day 168
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
Total number of self-reported injection drug use related events per total number of participant days at risk.	Assessment of Infectious or Other Complications of Injection Drug Use assess for self-report of skin or soft-tissue infections, osteoarticular infections (septic arthritis, osteomyelitis, epidural abscess), endovascular infections including endocarditis, or new injection-related viral infections.	Up to Day 168
Pain measured using PEG-3: "Pain average," "interference with Enjoyment of life," and "interference with General activity."	Mean scores on the PEG-3 screening instrument over time. Total score range is 0-10; the highest being the worse pain.	Up to Day 168
Number of self-reported days with acute care utilization (ED or hospitalization) events during the 168 days post-randomization per month.	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

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 (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 1, 2029

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): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Opioid Use Disorder; Methadone; Buprenorphine
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-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; 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