Opioid-use DisorderPhase 2NCT04225598
Emergency Department-Initiated Buprenorphine Validation Network Trial
A Phase 2 study testing CAM2038 and Buprenorphine Sublingual Product in people with Opioid-use Disorder, run by Yale University at 35 sites in United States.
Trial summary
This study will (1) recruit, train and provide resources to approximately 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to provide ED-initiated buprenorphine (BUP) for patients presenting with opioid use disorder (OUD) who are not receiving medications for opioid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid-use Disorder
- What is being tested?
- CAM2038 and Buprenorphine Sublingual Product
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 35 sitesUnited States
- Study dates
- 8 Jul 2020to 6 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be 18 years or older
- Treated in the ED during study screening hours
- Meet DSM-5 (Diagnostic and Statistical Manual) diagnostic criteria for moderate to severe OUD
- Have a COWS score of > or equal to 4
- Have a urine toxicology test that is positive for opioids (opiates, oxycodone, buprenorphine). Patients with urines that are only positive for fentanyl will be eligible if their clinical history and physical exam are consistent with opioid use and they meet DSM-5 criteria for moderate to severe OUD.
- Able to speak English sufficiently to understand the study the study procedures and provide written informed consent to participate in the study. (Exception may be made if sites with large population of Spanish speaking patients are accepted for participation in the study and study materials are translated into Spanish. Translated study materials will be reviewed and approved by the Institutional Review Board) IRB of record prior to use.)
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- Be 18 years or older
- Treated in the ED during study screening hours
- Meet DSM-5 diagnostic criteria for moderate to severe opioid use disorder
- Have a COWS <8
- Have a urine toxicology test that is positive for opioids (opiates, oxycodone, or buprenorphine). Patients with urines that are only positive for fentanyl on the point of care test strip will be eligible if their clinical history and physical exam are consistent with opioid use and they meet DSM-5 criteria for moderate to severe OUD.
- Be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study
Who cannot join
- Have urine toxicology test that is positive for methadone
- Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
- Have a medical or psychiatric condition that requires hospitalization
- Opioid administration (excluding BUP) at the index ED visit, prior to enrollment, and COWS remains < 8 during ED stay
- Be actively suicidal or severely cognitively impaired precluding informed consent
- Present from an extended care facility (e.g., skilled nursing facility)
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- Require continued prescription opioids for a pain condition
- Be a prisoner or in police custody at the time of index ED visit
- Be currently (anytime within the past 14 days) enrolled in formal addiction treatment, including by court order. Patients enrolled in formal addiction who are not receiving MOUD are eligible
- Be unable to provide reliable locator information including 2 contact numbers in addition to their own
- 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 component
- Ancillary Component:
- Have a urine toxicology test that is positive for methadone
- Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
- Have a medical or psychiatric condition that requires hospitalization at the index ED visit, prior to enrollment
- Be actively suicidal or severely cognitively impaired precluding informed consent
- Present from an extended care facility (e.g., skilled nursing facility)
- Require continued prescription opioids for a pain condition
- Be a prisoner or in police custody at the time of index ED visit
- Be currently (anytime within the past 7 days) enrolled in formal addiction treatment, including by court order. Patients enrolled in formal addiction treatment but are not receiving MOUD are eligible
- Be unable to provide reliable locator information including 2 contact numbers in addition to their own
- Be unwilling to follow study procedures (e.g., unwilling to provide permission to answer daily assessments until day 7)
- Have prior enrollment in the current study
Trial locations and contacts
35 sites in 1 country.
35 sites in 1 country
United States35 sites
Presybterian Hospital, Albuquerque, NM
Albuquerque, New Mexico, 87106
University of New Mexico Hospital
Albuquerque, New Mexico, 87106
Grady Memorial Hospital
Atlanta, Georgia, 30303
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Cooper University Hospital
Camden, New Jersey, 08103
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Chicago Medicine
Chicago, Illinois, 60637
Parkland Memorial Hospital
Dallas, Texas, 75235
Detroit Receiving Hospital
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Duke University
Durham, North Carolina, 27710
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
West Virginia University - Berkeley Medical Center
Martinsburg, West Virginia, 25401
Jackson Memorial Hospital
Miami, Florida, 33136
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale New Haven Health (Yale New Haven Hospital)
New Haven, Connecticut, 06510
Bellevue Hospital
New York, New York, 10016
Icahn School of Medicine
New York, New York, 10029
Columbia University Irving Medical Center- NY Presbyterian
New York, New York, 10032
Weill Cornell Medical College
New York, New York, 10065
Highland Hospital
Oakland, California, 94602
Pennsylvania Presbyterian Medical Center/Hospital of UPENN
Philadelphia, Pennsylvania, 19104
Temple University Hospital - Episcopal Campus
Philadelphia, Pennsylvania, 19125
UPMC Mercy Hospital
Pittsburgh, Pennsylvania, 15219
Maine Medical Center
Portland, Maine, 04102
Rhode Island Hospital/The Miriam Hospital
Providence, Rhode Island, 02903
University of Utah Hospital
Salt Lake City, Utah, 84132
San Leandro Hospital
San Leandro, California, 94578
University of Washington Medical Center- Harborview/Montlake
Seattle, Washington, 98195
Barnes Jewish Hospital
St Louis, Missouri, 63110
Upstate Medical University
Syracuse, New York, 13210
Tampa General Hospital
Tampa, Florida, 33606
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27101
About this study
This study will (1) recruit, train and provide resources to approximately 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to provide ED-initiated buprenorphine (BUP) for patients presenting with opioid use disorder (OUD) who are not receiving medications for opioid use disorder (MOUD). Once implementation is adequately achieved, the sites will (2) conduct a randomized controlled trial (RCT) to compare the effectiveness of sublingual buprenorphine (SL-BUP) versus extended-release buprenorphine (XR-BUP) on ED patients' engagement in formal addiction treatment 7-days after their ED visit. In addition, in an ancillary component of the study, the investigators will (3) assess the use of XR-BUP in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores < 8 in a case series to potentially expand the eligibility of patients in the larger RCT to those presenting with little to no opioid withdrawal symptoms. Finally, the investigators will (4) develop and validate ED electronic health record (EHR) opioid-related phenotypes, both of which will inform the main RCT.
Read the detailed description
The study will be comprised of four components as outlined below:
- Site implementation component: In this component, the investigators will use previously developed implementation facilitation strategies and resources to train ED providers and staff at approximately 30 diverse EDs in treatment initiation with SL-BUP and XR-BUP and develop ED buprenorphine protocols and procedures. The investigators anticipate that this will result in a minimum of 24 sites (80%) that will meet the implementation milestones for competence in ED-initiated BUP using standard SL and XR-BUP inductions.
- Effectiveness RCT component: This component is a large pragmatic RCT using a Hybrid Type 1 Effectiveness-Implementation design. Sites that satisfactorily complete the site implementation component will be activated on a rolling basis for the RCT after demonstrated implementation milestones have been met. In this Hybrid Type 1 design the primary research question is the effectiveness of SL-BUP induction compared with that of XR-BUP on the primary outcome measure of engagement in formal addiction treatment at 7-days post ED visit. This design also allows us to gather information and report on implementation processes.
- Ancillary component - XR-BUP Induction for patients with COWS < 8: This observational case series will begin in advance of the Effectiveness RCT component at approximately 4 ED sites with extensive experience in ED-initiated BUP. The investigators will collect quantitative and qualitative data on the use of XR-BUP in ED patients with low COWS scores for approximately 75 patients. Sites will receive a supply of XR-BUP for provision to up to 5 patients with a COWS score > 8. The purpose is to pre-study the procedures at the four ancillary study sites on treating OUD patients with XR-BUP prior to initiation of the ancillary component. Data collected from this pre-study will not be included in the analysis of the ancillary and effectiveness RCT component. These initial up to 20 pre-study patients will meet all other study criteria and undergo all assessments. It is anticipated that the information collected from the 75 patients in the ancillary component will allow for modification to the larger Effectiveness RCT by expanding eligibility criteria to include patients with COWS <8.
- Development and validation of EHR ED opioid-related phenotypes component: In this component, the investigators will develop EHR phenotypes of opioid-related illnesses that accurately and automatically characterize patient conditions, enhance the ability to actively monitor and surveil, and better identify representative samples and patients potentially eligible for study inclusion, leading ultimately to an enhanced inclusion and understanding of opioid-related conditions. At the primary Yale New Haven Health System sites, the phenotypes (rules- and machine learning-based) will be iteratively developed and internally validated. The rules-based phenotype will be mapped to a common data model and externally validated at 4 trial sites.
- An exploratory outcome of this study will be to assess the impact of COVID-19 on ED use for opioid-related diagnoses using EHR data.
The primary focus of this clinicaltrials.gov registration are the RCT outcomes. Implementation and ancillary outcomes will be identified as secondary outcomes for the purpose of this clinicaltrials.gov registration
- Conditions
- Opioid-use Disorder
- Being tested
- CAM2038, Buprenorphine Sublingual Product
- Keywords
- Opioid-use Disorder
- 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.
CAM2038Drug
Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.
Buprenorphine Sublingual ProductDrug
COWS ≥ 8: Patients will receive 4mg of SL-BUP for a COWS score of 8-12 (mild withdrawal). After 30-45 minutes if tolerated and no unanticipated adverse reactions, an additional 4mg can be administered for a total of 8mg in the ED. Patients presenting with moderate-severe withdrawal (COWS >≥ 13) will receive an initial dose of 8mg SL-BUP. All patients will receive a buprenorphine prescription and instructions for additional BUP doses to allow for up to a dose of 12mg if needed, and for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD (medications for opioid use disorder).
COWS 4-7: Patients will be provided with a uniform set of instructions to guide unobserved (home) induction. They will be prescribed doses of SL-BUP to allow them to take dose up to 12mg in the 24 hours after discharge. All patients will also receive a buprenorphine prescription for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD.
| Study group | Role | What they receive |
|---|---|---|
| XR-BUP | Experimental | Injectable buprenorphine Receives: Drug: CAM2038 |
| Standard SL-BUP | Active comparator | Sublingual buprenorphine Receives: Drug: Buprenorphine Sublingual Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization
Engagement in formal addiction treatment will be defined as enrollment and receiving formal addiction treatment on the 7th day post randomization, confirmed by contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, opioid treatment programs (OTPs), intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD at 7 days to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics Anonymous (AA) or (Narcotics Anonymous) NA alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
Measured: 7 days post randomization
Secondary outcomes (12)
RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization
self-report verified with treatment provider(s)
Measured: 7 days post randomization
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization
Engagement in formal addiction treatment will be defined as enrollment in formal addiction treatment on the 30th day post randomization, confirmed by direct contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, OTPs, intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD on the 30th day post randomization to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics or Narcotics Anonymous alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
Measured: 30 days post randomization
RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization
self report verified with treatment provider(s)
Measured: 30 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization
The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
Measured: 7 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization
The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
Measured: 30 days post randomization
RCT Component: Craving scores at 7 days post randomization
The investigators will use visual analogue scales (VAS) to assess craving, desire to use opioids and need to use opioids with a scale of 0-100.
Measured: 7 days post randomization
RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization
A brief, structured interview regarding health care utilization (inpatient and outpatient) will be used, which collects 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).
Measured: 30 days post randomization
RCT Component: Patient satisfaction with BUP at 7 days post randomization
The investigators will modify the patient satisfaction scale where overall experience is rated from 1 to 5 (1 is completely ineffective and 5 is completely effective) and treatment characteristics are rated 1 to 7 (1 is not important and 7 is extremely important) based on previous published data.
Measured: 7 days post randomization
RCT Component: Overdose Events at 30 days post randomization
Assessment of past 30-day overdose events will be completed at 30 days post study enrollment. In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
Measured: 30 days post randomization
Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration
Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
Measured: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration
Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
Measured: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration
Assessment of Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration.
Measured: Within 1 hour post XR-BUP injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start8 Jul 2020
- Primary completion6 Dec 2024
- Study completion6 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,000 participants (actual)
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, Harvard Medical School (HMS and HSDM), University of Pennsylvania, NYU Langone Health, Icahn School of Medicine at Mount Sinai, Alameda Health System, Weill Medical College of Cornell University, National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Gail D'Onofrio, MD, MS, Principal investigator, Yale School of Medicine, Department of Emergency MedicineDavid Fiellin, MD, Principal investigator, Yale School of Medicine, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04225598
- Sponsor's protocol ID
- 2000026164
- Other IDs
- 2UG1DA015831-19
- Status last verified
- Jan 2025
- First submitted
- 20 Dec 2019
- Last updated
- 10 Jan 2025
- 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
D'Onofrio G, Herring AA, Hawk KF, Perrone J, Cowan E, McCormack RP, Dziura J, Matthews AG, Pantalon MV, Owens P, Martel S, Coupet E Jr, Lofwall MR, Walsh SL, Edelman EJ, Carpenter JE, Strout TD, Baumann MR, Anderson E, Barrett TW, Dorey A, Taillac P, Cochran G, Crandall CS, Wilson J, Manteuffel J, Cole JB, Whiteside LK, Jones C, Samuels E, Huntley K, Fiellin DA; ED INNOVATION Investigators. Emergency Department-Initiated Buprenorphine for Opioid Use Disorder: A Randomized Clinical Trial. JAMA. 2026 Mar 17;335(11):948-960. doi: 10.1001/jama.2025.27019.
PubMed 41670966D'Onofrio G, Herring AA, Perrone J, Hawk K, Samuels EA, Cowan E, Anderson E, McCormack R, Huntley K, Owens P, Martel S, Schactman M, Lofwall MR, Walsh SL, Dziura J, Fiellin DA. Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal. JAMA Netw Open. 2024 Jul 1;7(7):e2420702. doi: 10.1001/jamanetworkopen.2024.20702.
PubMed 38976265Snavely AC, Paradee BE, Ashburn NP, Allen BR, Christenson R, O'Neill JC, Nowak R, Wilkerson RG, Mumma BE, Madsen T, Stopyra JP, Mahler SA. Derivation and validation of a high sensitivity troponin-T HEART pathway. Am Heart J. 2023 Feb;256:148-157. doi: 10.1016/j.ahj.2022.11.012. Epub 2022 Nov 16.
PubMed 36400184
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emergency Department-Initiated Buprenorphine Validation Network Trial
- ClinicalTrials.gov ID
- NCT04225598
- Acronym / sponsor ID
- 2000026164
- Conditions
- Opioid-use Disorder
- Keywords
- Opioid-use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,000 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Drug Abuse Treatment Clinical Trials Network, The Emmes Company, LLC, Harvard Medical School (HMS and HSDM), University of Pennsylvania, NYU Langone Health, Icahn School of Medicine at Mount Sinai, Alameda Health System, Weill Medical College of Cornell University, National Institute on Drug Abuse (NIDA)
- Study start
- 8 Jul 2020 (actual)
- Primary completion
- 6 Dec 2024 (actual)
- Study completion
- 6 Dec 2024 (actual)
- First posted
- 13 Jan 2020 (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 will (1) recruit, train and provide resources to approximately 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to provide ED-initiated buprenorphine (BUP) for patients presenting with opioid use disorder (OUD) who are not receiving medications for opioid use disorder (MOUD). Once implementation is adequately achieved, the sites will (2) conduct a randomized controlled trial (RCT) to compare the effectiveness of sublingual buprenorphine (SL-BUP) versus extended-release buprenorphine (XR-BUP) on ED patients' engagement in formal addiction treatment 7-days after their ED visit. In addition, in an ancillary component of the study, the investigators will (3) assess the use of XR-BUP in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores < 8 in a case series to potentially expand the eligibility of patients in the larger RCT to those presenting with little to no opioid withdrawal symptoms. Finally, the investigators will (4) develop and validate ED electronic health record (EHR) opioid-related phenotypes, both of which will inform the main RCT.
Detailed description
The study will be comprised of four components as outlined below:
- Site implementation component: In this component, the investigators will use previously developed implementation facilitation strategies and resources to train ED providers and staff at approximately 30 diverse EDs in treatment initiation with SL-BUP and XR-BUP and develop ED buprenorphine protocols and procedures. The investigators anticipate that this will result in a minimum of 24 sites (80%) that will meet the implementation milestones for competence in ED-initiated BUP using standard SL and XR-BUP inductions.
- Effectiveness RCT component: This component is a large pragmatic RCT using a Hybrid Type 1 Effectiveness-Implementation design. Sites that satisfactorily complete the site implementation component will be activated on a rolling basis for the RCT after demonstrated implementation milestones have been met. In this Hybrid Type 1 design the primary research question is the effectiveness of SL-BUP induction compared with that of XR-BUP on the primary outcome measure of engagement in formal addiction treatment at 7-days post ED visit. This design also allows us to gather information and report on implementation processes.
- Ancillary component - XR-BUP Induction for patients with COWS < 8: This observational case series will begin in advance of the Effectiveness RCT component at approximately 4 ED sites with extensive experience in ED-initiated BUP. The investigators will collect quantitative and qualitative data on the use of XR-BUP in ED patients with low COWS scores for approximately 75 patients. Sites will receive a supply of XR-BUP for provision to up to 5 patients with a COWS score > 8. The purpose is to pre-study the procedures at the four ancillary study sites on treating OUD patients with XR-BUP prior to initiation of the ancillary component. Data collected from this pre-study will not be included in the analysis of the ancillary and effectiveness RCT component. These initial up to 20 pre-study patients will meet all other study criteria and undergo all assessments. It is anticipated that the information collected from the 75 patients in the ancillary component will allow for modification to the larger Effectiveness RCT by expanding eligibility criteria to include patients with COWS <8.
- Development and validation of EHR ED opioid-related phenotypes component: In this component, the investigators will develop EHR phenotypes of opioid-related illnesses that accurately and automatically characterize patient conditions, enhance the ability to actively monitor and surveil, and better identify representative samples and patients potentially eligible for study inclusion, leading ultimately to an enhanced inclusion and understanding of opioid-related conditions. At the primary Yale New Haven Health System sites, the phenotypes (rules- and machine learning-based) will be iteratively developed and internally validated. The rules-based phenotype will be mapped to a common data model and externally validated at 4 trial sites.
- An exploratory outcome of this study will be to assess the impact of COVID-19 on ED use for opioid-related diagnoses using EHR data.
The primary focus of this clinicaltrials.gov registration are the RCT outcomes. Implementation and ancillary outcomes will be identified as secondary outcomes for the purpose of this clinicaltrials.gov registration
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XR-BUP | Experimental | Drug: CAM2038Injectable buprenorphine |
| Standard SL-BUP | Active comparator | Drug: Buprenorphine Sublingual ProductSublingual buprenorphine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be 18 years or older
- Treated in the ED during study screening hours
- Meet DSM-5 (Diagnostic and Statistical Manual) diagnostic criteria for moderate to severe OUD
- Have a COWS score of > or equal to 4
- Have a urine toxicology test that is positive for opioids (opiates, oxycodone, buprenorphine). Patients with urines that are only positive for fentanyl will be eligible if their clinical history and physical exam are consistent with opioid use and they meet DSM-5 criteria for moderate to severe OUD.
Key exclusion criteria (24 listed)
- Have urine toxicology test that is positive for methadone
- Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
- Have a medical or psychiatric condition that requires hospitalization
- Opioid administration (excluding BUP) at the index ED visit, prior to enrollment, and COWS remains < 8 during ED stay
- Be actively suicidal or severely cognitively impaired precluding informed consent
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 |
|---|---|---|
| CAM2038Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0. | Drug | XR-BUP |
| Buprenorphine Sublingual ProductCOWS ≥ 8: Patients will receive 4mg of SL-BUP for a COWS score of 8-12 (mild withdrawal). After 30-45 minutes if tolerated and no unanticipated adverse reactions, an additional 4mg can be administered for a total of 8mg in the ED. Patients presenting with moderate-severe withdrawal (COWS >≥ 13) will receive an initial dose of 8mg SL-BUP. All patients will receive a buprenorphine prescription and instructions for additional BUP doses to allow for up to a dose of 12mg if needed, and for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD (medications for opioid use disorder). COWS 4-7: Patients will be provided with a uniform set of instructions to guide unobserved (home) induction. They will be prescribed doses of SL-BUP to allow them to take dose up to 12mg in the 24 hours after discharge. All patients will also receive a buprenorphine prescription for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD. | Drug | Standard SL-BUP |
Primary outcome
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization
Time frame: 7 days post randomization
Engagement in formal addiction treatment will be defined as enrollment and receiving formal addiction treatment on the 7th day post randomization, confirmed by contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, opioid treatment programs (OTPs), intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD at 7 days to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics Anonymous (AA) or (Narcotics Anonymous) NA alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
12 secondary outcomes
RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization
Time frame: 7 days post randomization
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization
Time frame: 30 days post randomization
RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization
Time frame: 30 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization
Time frame: 7 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization
Time frame: 30 days post randomization
RCT Component: Craving scores at 7 days post randomization
Time frame: 7 days post randomization
RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization
Time frame: 30 days post randomization
RCT Component: Patient satisfaction with BUP at 7 days post randomization
Time frame: 7 days post randomization
RCT Component: Overdose Events at 30 days post randomization
Time frame: 30 days post randomization
Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration
Time frame: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration
Time frame: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration
Time frame: Within 1 hour post XR-BUP injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
- Derived from this study: PubMed 41670966D'Onofrio G, Herring AA, Hawk KF, Perrone J, Cowan E, McCormack RP, Dziura J, Matthews AG, Pantalon MV, Owens P, Martel S, Coupet E Jr, Lofwall MR, Walsh SL, Edelman EJ, Carpenter JE, Strout TD, Baumann MR, Anderson E, Barrett TW, Dorey A, Taillac P, Cochran G, Crandall CS, Wilson J, Manteuffel J, Cole JB, Whiteside LK, Jones C, Samuels E, Huntley K, Fiellin DA; ED INNOVATION Investigators. Emergency Department-Initiated Buprenorphine for Opioid Use Disorder: A Randomized Clinical Trial. JAMA. 2026 Mar 17;335(11):948-960. doi: 10.1001/jama.2025.27019.
- Derived from this study: PubMed 38976265D'Onofrio G, Herring AA, Perrone J, Hawk K, Samuels EA, Cowan E, Anderson E, McCormack R, Huntley K, Owens P, Martel S, Schactman M, Lofwall MR, Walsh SL, Dziura J, Fiellin DA. Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal. JAMA Netw Open. 2024 Jul 1;7(7):e2420702. doi: 10.1001/jamanetworkopen.2024.20702.
- Derived from this study: PubMed 36400184Snavely AC, Paradee BE, Ashburn NP, Allen BR, Christenson R, O'Neill JC, Nowak R, Wilkerson RG, Mumma BE, Madsen T, Stopyra JP, Mahler SA. Derivation and validation of a high sensitivity troponin-T HEART pathway. Am Heart J. 2023 Feb;256:148-157. doi: 10.1016/j.ahj.2022.11.012. Epub 2022 Nov 16.
- 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. This study is not recruiting at the moment.
Gail D'Onofrio, MD, MS principal investigator
Yale School of Medicine, Department of Emergency Medicine
David Fiellin, MD principal investigator
Yale School of Medicine, Department of Internal Medicine
35 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CAM2038 and Buprenorphine Sublingual Product in people with Opioid-use Disorder, run by Yale University at 35 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 12 inclusion and 24 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: finished, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization (time frame: 7 days post 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 NCT04225598, which also lists 3 linked publications.
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 10 Jan 2025.