Opioid Use DisorderPhase 3ED-ENVISIONNCT06494904
Standard Versus High Dose ED-Initiated Buprenorphine Induction
A Phase 3 study testing Buprenorphine in people with Opioid Use Disorder, run by Yale University at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Buprenorphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 5 sitesUnited States
- Study dates
- 6 Dec 2024to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Cooper University Hospital
Camden, New Jersey, 08103
Christopher Jones, MD, Jones-Christopher@CooperHealth.edu
Christopher Jones
- Recruiting
Highland Hospital
Oakland, California, 94602
Andrew Herring, MD, 510-437-4800, aherring@alamedahealthsystem.org
Andrew Herring, MD
- Recruiting
Maine Medical Center
Portland, Maine, 04102
Tania Strout, PhD, RN, MS, Tania.Strout@mainehealth.org
Michael Baumann, MD
- Recruiting
University of Utah Hospital
Salt Lake City, Utah, 84132
Alyrene Dorey, MD, Alyrene.Dorey@hsc.utah.edu
Alyrene Dorey, MD
- Recruiting
San Leandro Hospital
San Leandro, California, 94578
Erik S Anderson, MD, 510-437-4970, esanderson@alamedahealthsystem.org
Erik Anderson, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Opioid Use Disorder
- Being tested
- Buprenorphine
- Keywords
- Buprenorphine, Substance use disorder treatment
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Also called Zubsolv
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.
| Study group | Role | What they receive |
|---|---|---|
| High Dose SL-BUP | Experimental | Participants will receive three 5.7 mg Zubsolv pills; all will be active medication. Receives: 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. Receives: Drug: Buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 10 days after study randomization
Secondary outcomes (4)
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: 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: 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: 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
Measured: Within 30 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2024
- Study start6 Dec 2024
- Primary completionSep 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 360 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Drug Abuse Treatment Clinical Trials Network, The Emmes Company, LLC, National Institute on Drug Abuse (NIDA), Alameda Health System
- Responsible party
- Sponsor
- Investigators
- Gail D'Onofrio, MD, MS, Principal investigator, Yale UniversityKathryn Hawk, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06494904
- Sponsor's protocol ID
- UG1DA015831
- Other IDs
- UG1DA015831
- Acronym
- ED-ENVISION
- Status last verified
- May 2026
- First submitted
- 2 Jul 2024
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Hawk K, Herring A, Chawarski M, Anderson ES, Baumann M, Dorey A, Holtyn AF, Jones C, Martel S, Owens P, Kmiecik K, Strout TD, Taillac P, Lofwall M, Walsh SL, D'Onofrio G. Emergency Department-initiated standard versus high-dose buprenorphine induction (ENVISION): a randomised clinical trial protocol. BMJ Open. 2026 Jun 3;16(6):e113762. doi: 10.1136/bmjopen-2025-113762.
PubMed 42236100
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ED-Initiated Standard Versus High Dose Buprenorphine Induction
- ClinicalTrials.gov ID
- NCT06494904
- Acronym / sponsor ID
- ED-ENVISION / UG1DA015831
- Conditions
- Opioid Use Disorder
- Keywords
- Buprenorphine, Substance use disorder treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 360 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Drug Abuse Treatment Clinical Trials Network, The Emmes Company, LLC, National Institute on Drug Abuse (NIDA), Alameda Health System
- Study start
- 6 Dec 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 10 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Dose SL-BUP | Experimental | Drug: BuprenorphineParticipants will receive three 5.7 mg Zubsolv pills; all will be active medication. |
| Standard SL-BUP | Active comparator | Drug: BuprenorphineParticipants will receive three pills; one 5.7 mg Zubsolv pill with active medication and two placebo pills. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuprenorphineAlso: ZubsolvAll 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. | Drug | High Dose SL-BUP, Standard SL-BUP |
Primary outcome
Engagement in Treatment (10)
Time frame: Within 10 days after study randomization
The proportion of patients in each of the two study arms participating in OUD treatment within 10 days after the study randomization
4 secondary outcomes
Craving
Time frame: Measured daily for 10 days post randomization
Withdrawal
Time frame: Measured daily for 10 days post randomization
Substance Use
Time frame: Measured daily for 10 days post randomization
Engagement in Treatment (30)
Time frame: Within 30 days after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Derived from this study: PubMed 42236100Hawk K, Herring A, Chawarski M, Anderson ES, Baumann M, Dorey A, Holtyn AF, Jones C, Martel S, Owens P, Kmiecik K, Strout TD, Taillac P, Lofwall M, Walsh SL, D'Onofrio G. Emergency Department-initiated standard versus high-dose buprenorphine induction (ENVISION): a randomised clinical trial protocol. BMJ Open. 2026 Jun 3;16(6):e113762. doi: 10.1136/bmjopen-2025-113762.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gail D'Onofrio, MD, MS principal investigator
Yale University
Kathryn Hawk principal investigator
Yale University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Buprenorphine in people with Opioid Use Disorder, run by Yale University at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gail D'Onofrio, MD, MS (2037857059, gail.donofrio@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engagement in Treatment (10) (time frame: Within 10 days after study randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06494904, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.