Comparing Outpatient Treatment Retention Among Individuals Using Fentanyl Randomized to Low-dose and Direct-to-inject Buprenorphine Initiation

NCT07469501 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 1K23DA060329-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pragmatic randomized controlled trial is to compare treatment outcomes of two strategies for initiating buprenorphine treatment (low-dose initiation and direct-to-inject) in adults with opioid use disorder (OUD) who use fentanyl. This study aims to:

1. 1.Compare effectiveness of each strategy on treatment retention in a real world, clinical setting, and
2. 2.Assess differences between strategies in patient-reported outcomes, including withdrawal symptoms, cravings, drug use, treatment satisfaction, and overall acceptability.
3. 3.Be randomized to initiate buprenorphine via a low-dose initiation or direct-to-inject protocol at an outpatient buprenorphine clinic,
4. 4.Keep a diary of craving and withdrawal symptoms for the first 7 days after initiation, and
5. 5.Visit the outpatient clinic 7, 30, and 90 days after initiation for urinary drug screen and follow-up surveys.

Conditions

Opioid Use Disorder; Fentanyl

Keywords

Buprenorphine initiation; Low-dose initiation; Direct-to-inject initiation; Medication for opioid use disorder; Outpatient treatment for opioid use disorder

Outcome Measures

Primary Outcomes (2)

• Continuous retention in outpatient buprenorphine treatment by day 90

  Receiving continuous treatment with buprenorphine sublingual prescriptions or injections administrations during the 90 days of follow up post-randomization as intended-to-treat. A period without buprenorphine treatment ≥8 days will be considered treatment discontinuation. Number of days of continuous treatment with the site clinician prescribing sublingual or injectable buprenorphine treatment during the 90 days post-randomization among RCT participants

  90 days

• Self-reported protocol satisfaction at day 7

  Patient-reported satisfaction with buprenorphine initiation protocol measured by Likert-scale satisfaction survey administered on day 7 follow-up visit

  7 days

Secondary Outcomes (16)

• Per protocol and as-treated retention in outpatient buprenorphine treatment at day 90

  90 days

• Successful buprenorphine initiation within first 7 days

  7 days

• Fentanyl use during days 1-7 determiend by urinary drug screen

  7 days

• Fentanyl use during days 8-30 determined by urinary drug screen

  30 days

• Fentanyl use during days 31-90 determined by urinary drug screen

  90 days

Other Outcomes (5)

• Overall number of adverse events in each arm within 30 days, and by relatedness to study intervention

  30 days

• Number of serious adverse events in each arm in 30 days, and by relatedness to the study intervention

  30 days

• Number of ED visits and hospital admissions in each arm in 30 days, and by relatedness to study intervention

  30 days

Study Arms (2)

Low-dose initiation (LDI)

ACTIVE COMPARATOR

Participants start 0.5mg sublingual buprenorphine (Subutex) and gradually increase by 0.5-1.0mg daily for 7 days

Drug: Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)

Direct-to-inject (DTI)

EXPERIMENTAL

Participants receive 8-32mg long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly injections as discussed with the provider

Drug: Injectable buprenorphine

Interventions

Injectable buprenorphine DRUG

Starting dose (8-32mg) of long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly maintenance doses (e.g., 128mg Brixadi or 300mg Sublocade)

Also known as: Direct-to-inject, Brixadi, Sublocade, Long-acting injectable buprenorphine

Direct-to-inject (DTI)

Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets) DRUG

Starting dose (0.5mg) of sublingual buprenorphine tablets in blister packs (Brixadi or Sublocade) on day 1, followed by 0.5-1.0mg daily increases in week 1 and maintenance dosing based on shared decision-making with provider

Also known as: Low-dose buprenorphine initiation, Suboxone, Buprenorphine blister packs

Low-dose initiation (LDI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age at Visit 1.
• Documentation of an OUD diagnosis as evidenced by meeting two or more of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) Criteria for Opioid Use Disorder
• Self-reported daily use of fentanyl ≥ 5 out of the past 7 days at baseline,
• Fentanyl-positive urine drug screening at baseline,
• Interest in stopping or reducing fentanyl use,
• Publicly insured through San Francisco Medicaid or Medicare and therefore able receive buprenorphine prescription dispensing through Community Behavioral Health Services (CBHS) Pharmacy

You may not qualify if:

• Currently nursing, pregnant, or anticipating pregnancy in the next 6 months
• Methadone-positive urine drug screening at baseline
• Buprenorphine-positive urine drug screening at baseline
• Be unable to provide any locator or contact information at least one contact in addition to themselves
• Any pending legal action that could prevent participation in study activities
• Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data (e.g., acute psychosis), or cognitive impairment (e.g., dementia)

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

San Francisco Outpatient Buprenorphine Induction Clinic

San Francisco, California, 94103, United States

Location

Related Publications (2)

• Noel M, Abbs E, Suen L, Samuel L, Dobbins S, Geier M, Soran CS. The Howard Street Method: A Community Pharmacy-led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl. J Addict Med. 2023 Jul-Aug 01;17(4):e255-e261. doi: 10.1097/ADM.0000000000001154. Epub 2023 Feb 17.

  PMID: 37579105 BACKGROUND

• Rosenwohl-Mack S, Suen LW, Logan AA, Peterson D, Snyder HR. Outpatient Initiation of 7-Day Injectable Buprenorphine: A Direct-to-Inject Case Series. Subst Use Addctn J. 2025 Oct;46(4):1064-1069. doi: 10.1177/29767342251330412. Epub 2025 Apr 4.

  PMID: 40183345 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine; Sublocade; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Leslie W Suen, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leslie W Suen, MD

CONTACT

628-206-6007; leslie.suen@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2026
• First Posted: March 13, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)