Standard Versus High Dose ED-Initiated Buprenorphine Induction

NCT06494904 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: UG1DA015831
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a multisite double-blind, double-dummy, randomized clinical trial enrolling ED patients with untreated moderate to severe opioid use disorder (OUD) to compare Standard Dose Induction (SDI) and High Dose Induction (HDI) on rates of participation in OUD treatment within 10 days post randomization, and opioid withdrawal symptoms, opioid craving, and use of illicit and non-prescribed drugs.

Conditions

Opioid Use Disorder

Keywords

Buprenorphine; Substance use disorder treatment

Outcome Measures

Primary Outcomes (1)

• Engagement in Treatment (10)

  The proportion of patients in each of the two study arms participating in OUD treatment within 10 days after the study randomization

  Within 10 days after study randomization

Secondary Outcomes (4)

• Craving

  Measured daily for 10 days post randomization

• Withdrawal

  Measured daily for 10 days post randomization

• Substance Use

  Measured daily for 10 days post randomization

• Engagement in Treatment (30)

  Within 30 days after randomization

Study Arms (2)

High Dose SL-BUP

EXPERIMENTAL

Participants will receive three 5.7 mg Zubsolv pills; all will be active medication.

Drug: Buprenorphine

Standard SL-BUP

ACTIVE COMPARATOR

Participants will receive three pills; one 5.7 mg Zubsolv pill with active medication and two placebo pills.

Drug: Buprenorphine

Interventions

Buprenorphine DRUG

All patients will receive 3 pills and will be observed for 2 hours post-study medication administration with repeated COWS at approximately hours 1 and 2. All participants will be given a referral for ongoing MOUD and will be discharged with a prescription for 16 mg daily of buprenorphine daily.

Also known as: Zubsolv

High Dose SL-BUP; Standard SL-BUP

Eligibility Criteria

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

You may qualify if:

• All patients enrolled into the study must:
• Be 18-65 years of age.
• Be treated in the ED during study screening hours.
• Meet DSM-5 diagnostic criteria for moderate to severe OUD.
• Have a Clinical Opiate Withdrawal Scale (COWS) score of ≥8 at enrollment (including 2 objective signs of withdrawal at enrollment).
• Have a urine toxicology test that is positive for opioids.
• Be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.

You may not qualify if:

• All patients enrolled into the study must not:
• Have a medical or psychiatric condition that requires hospitalization at the time of index ED visit.
• Have a known hypersensitivity reaction to buprenorphine/naloxone
• Be actively suicidal or severely cognitively impaired precluding informed consent.
• Require ongoing prescription for opioid analgesics.
• Have a physical exam or reported history consistent with severe liver failure
• Have a positive urine test for methadone and reported use in the past 72 hours
• Be a prisoner or in police custody at the time of index ED visit.
• Be unwilling to follow study procedures (e.g., unwilling to provide permission to contact referral provider/program or unavailable for the follow-up assessments)
• Have prior enrollment in the current study.
• Receiving MOUD treatment within the past 7 days.
• Be pregnant as determined by human gonadotropin (hCG) testing at the index ED visit
• Have a respiratory rate \<8 or oxygen saturation \<93%
• Be a participant in any other clinical trial in which medications are being delivered or the use of an investigational drug or device within the last 30 days

Sponsors & Collaborators

• Yale University: lead
• National Drug Abuse Treatment Clinical Trials Network: collaborator
• The Emmes Company, LLC: collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• Alameda Health System: collaborator

Study Sites (5)

Highland Hospital

Oakland, California, 94602, United States

RECRUITING

San Leandro Hospital

San Leandro, California, 94578, United States

RECRUITING

Maine Medical Center

Portland, Maine, 04102, United States

RECRUITING

Cooper University Hospital

Camden, New Jersey, 08103, United States

RECRUITING

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine; 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

• Gail D'Onofrio, MD, MS

  Yale University

  PRINCIPAL INVESTIGATOR

• Kathryn Hawk

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gail D'Onofrio, MD, MS

CONTACT

2037857059; gail.donofrio@yale.edu

Kathryn Hawk, MD, MHS

CONTACT

2037857899; kathryn.hawk@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is a multi-site double-blind, double-dummy randomized clinical trial. Only the DSC staff overseeing the random assignment schedule, a few designated CCC staff, and the central research staff preparing the study medication will be unblinded; all other study personnel and participants will remain blinded to treatment arm until the nationwide completion of the trial and the database is formally locked. Detailed information on the study procedures regarding the double-blinding will be contained in a standalone Blinding Management Plan and Study Site Blinding Plan. A DSMB will review study data throughout the course of the trial in a blinded fashion (e.g., masked treatment assignments), however they can request to be unblinded at any time.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: July 10, 2024
• Study Start: December 6, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be made 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.
• Access Criteria: De-identified scientific data generated from this study will be available to the public in the NIDA data repository, per NIDA CTN policy and the Data Management and Sharing Plan for this study.

Locations

US (5)