Emergency Department-Initiated Buprenorphine Validation Network Trial

NCT ID: NCT04225598

Last Updated: 2025-01-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

2000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-08

Study Completion Date

2024-12-06

Brief Summary

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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

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The study will be comprised of four components as outlined below:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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

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Opioid-use Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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XR-BUP

Injectable buprenorphine

Group Type EXPERIMENTAL

CAM2038

Intervention Type DRUG

Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.

Standard SL-BUP

Sublingual buprenorphine

Group Type ACTIVE_COMPARATOR

Buprenorphine Sublingual Product

Intervention Type DRUG

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.

Interventions

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CAM2038

Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.

Intervention Type DRUG

Buprenorphine Sublingual Product

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Be 18 years or older
2. Treated in the ED during study screening hours
3. Meet DSM-5 (Diagnostic and Statistical Manual) diagnostic criteria for moderate to severe OUD
4. Have a COWS score of \> or equal to 4
5. 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.
6. 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.)


1. Be 18 years or older
2. Treated in the ED during study screening hours
3. Meet DSM-5 diagnostic criteria for moderate to severe opioid use disorder
4. Have a COWS \<8
5. 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.
6. Be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study

Exclusion Criteria

1. Have urine toxicology test that is positive for methadone
2. Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
3. Have a medical or psychiatric condition that requires hospitalization
4. Opioid administration (excluding BUP) at the index ED visit, prior to enrollment, and COWS remains \< 8 during ED stay
5. Be actively suicidal or severely cognitively impaired precluding informed consent
6. Present from an extended care facility (e.g., skilled nursing facility)
7. Require continued prescription opioids for a pain condition
8. Be a prisoner or in police custody at the time of index ED visit
9. 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
10. Be unable to provide reliable locator information including 2 contact numbers in addition to their own
11. Be unwilling to follow study procedures (e.g., unwilling to provide permission to contact referral provider/program or unavailable for the follow-up assessments)
12. Have prior enrollment in the current study component

Ancillary Component:


1. Have a urine toxicology test that is positive for methadone
2. Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
3. Have a medical or psychiatric condition that requires hospitalization at the index ED visit, prior to enrollment
4. Be actively suicidal or severely cognitively impaired precluding informed consent
5. Present from an extended care facility (e.g., skilled nursing facility)
6. Require continued prescription opioids for a pain condition
7. Be a prisoner or in police custody at the time of index ED visit
8. 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
9. Be unable to provide reliable locator information including 2 contact numbers in addition to their own
10. Be unwilling to follow study procedures (e.g., unwilling to provide permission to answer daily assessments until day 7)
11. Have prior enrollment in the current study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Drug Abuse Treatment Clinical Trials Network

NETWORK

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role collaborator

Alameda Health System

OTHER

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gail D'Onofrio, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Yale School of Medicine, Department of Emergency Medicine

David Fiellin, MD

Role: PRINCIPAL_INVESTIGATOR

Yale School of Medicine, Department of Internal Medicine

Locations

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Highland Hospital

Oakland, California, United States

Site Status

San Leandro Hospital

San Leandro, California, United States

Site Status

Yale New Haven Health (Yale New Haven Hospital)

New Haven, Connecticut, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Chicago Medicine

Chicago, Illinois, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Detroit Receiving Hospital

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Barnes Jewish Hospital

St Louis, Missouri, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Presybterian Hospital, Albuquerque, NM

Albuquerque, New Mexico, United States

Site Status

University of New Mexico Hospital

Albuquerque, New Mexico, United States

Site Status

Bellevue Hospital

New York, New York, United States

Site Status

Icahn School of Medicine

New York, New York, United States

Site Status

Columbia University Irving Medical Center- NY Presbyterian

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Upstate Medical University

Syracuse, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Wake Forest School of Medicine

Winston-Salem, North Carolina, United States

Site Status

Pennsylvania Presbyterian Medical Center/Hospital of UPENN

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital - Episcopal Campus

Philadelphia, Pennsylvania, United States

Site Status

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital/The Miriam Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Parkland Memorial Hospital

Dallas, Texas, United States

Site Status

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status

University of Washington Medical Center- Harborview/Montlake

Seattle, Washington, United States

Site Status

West Virginia University - Berkeley Medical Center

Martinsburg, West Virginia, United States

Site Status

Countries

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United States

References

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D'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.

Reference Type DERIVED
PMID: 38976265 (View on PubMed)

Snavely 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.

Reference Type DERIVED
PMID: 36400184 (View on PubMed)

Other Identifiers

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2UG1DA015831-19

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000026164

Identifier Type: -

Identifier Source: org_study_id

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