Standard Versus High Dose ED-Initiated Buprenorphine Induction (ED-ENVISION)

ED-Initiated Standard Versus High Dose Buprenorphine Induction

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Buprenorphine

Detailed Description

This study will recruit, train, and provide resources to approximately 4 ED systems throughout the U.S. to recruit ED patients presenting with OUD not receiving medications for opioid use disorder (MOUD) as part of an RCT to compare SDI (Zubsolv 5.7/1.4 mg buprenorphine/naloxone* plus 2 placebo tablets) with HDI (three Zubsolv 5.7/1.4 mg* buprenorphine/naloxone tablets) to evaluate rate of participation in OUD treatment within 10 days post-randomization and differences in outcomes of tolerability, opioid withdrawal symptoms, craving, and use of illicit drugs.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gail D'Onofrio, MD, MS; Phone Number: 2037857059; Email: gail.donofrio@yale.edu
• Study Contact Backup: Name: Kathryn Hawk, MD, MHS; Phone Number: 2037857899; Email: kathryn.hawk@yale.edu

Study Locations

• United States
  • California
    • Oakland, California, United States, 94602
      • Recruiting
      • Highland Hospital
      • Contact: Andrew Herring, MD; Phone Number: 510-437-4800; Email: aherring@alamedahealthsystem.org
      • Principal Investigator: Andrew Herring, MD
    • San Leandro, California, United States, 94578
      • Recruiting
      • San Leandro Hospital
      • Principal Investigator: Erik Anderson, MD
      • Contact: Erik S Anderson, MD; Phone Number: 510-437-4970; Email: esanderson@alamedahealthsystem.org
  • Maine
    • Portland, Maine, United States, 04102
      • Recruiting
      • Maine Medical Center
      • Principal Investigator: Michael Baumann, MD
      • Contact: Tania Strout, PhD, RN, MS; Email: Tania.Strout@mainehealth.org
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Recruiting
      • Cooper University Hospital
      • Principal Investigator: Christopher Jones
      • Contact: Christopher Jones, MD; Email: Jones-Christopher@CooperHealth.edu
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah Hospital
      • Contact: Alyrene Dorey, MD; Email: Alyrene.Dorey@hsc.utah.edu
      • Principal Investigator: Alyrene Dorey, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

All patients enrolled into the study must:

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

Exclusion Criteria:

All patients enrolled into the study must not:

1. Have a medical or psychiatric condition that requires hospitalization at the time of index ED visit.
2. Have a known hypersensitivity reaction to buprenorphine/naloxone
3. Be actively suicidal or severely cognitively impaired precluding informed consent.
4. Require ongoing prescription for opioid analgesics.
5. Have a physical exam or reported history consistent with severe liver failure
6. Have a positive urine test for methadone and reported use in the past 72 hours
7. Be a prisoner or in police custody at the time of index ED visit.
8. Be unwilling to follow study procedures (e.g., unwilling to provide permission to contact referral provider/program or unavailable for the follow-up assessments)
9. Have prior enrollment in the current study.
10. Receiving MOUD treatment within the past 7 days.
11. Be pregnant as determined by human gonadotropin (hCG) testing at the index ED visit
12. Have a respiratory rate <8 or oxygen saturation <93%
13. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose SL-BUP; Participants will receive three 5.7 mg Zubsolv pills; all will be active medication.	Drug: Buprenorphine; 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.; Other Names: Zubsolv
Active Comparator: Standard SL-BUP; Participants will receive three pills; one 5.7 mg Zubsolv pill with active medication and two placebo pills.	Drug: Buprenorphine; 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.; Other Names: Zubsolv

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Craving	The maximum intensity of opioid cravings during the preceding 24 hours assessed daily for 10 days post randomization using a numerical rating scale (0 to 10).	Measured daily for 10 days post randomization
Withdrawal	The maximum intensity of opioid withdrawal symptoms during the preceding 24 hours assessed daily for 10 days post randomization using a numerical rating scale (0 to 10).	Measured daily for 10 days post randomization
Substance Use	The number of days with illicit opioid and other substance use based on self-reported data obtained daily during the first 10 days post randomization	Measured daily for 10 days post randomization
Engagement in Treatment (30)	The proportion of patients in each of the two study arms participating in OUD treatment	Within 30 days after randomization

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); The Emmes Company, LLC; National Drug Abuse Treatment Clinical Trials Network; Alameda Health System
• Investigators: Principal Investigator: Gail D'Onofrio, MD, MS, Yale University; Principal Investigator: Kathryn Hawk, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Buprenorphine; Substance use disorder treatment
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Drug Combinations; Naloxone; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Buprenorphine, Naloxone Drug Combination; Buprenorphine
• Other Study ID Numbers: UG1DA015831 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In line with the National Institutes of Health Helping to End Addiction Long-term (NIH HEAL) Initiative Public Access and Data Sharing Policy, publications and underlying primary data will be made available to the public.
• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No