Emergency Department-Initiated Buprenorphine Validation Network Trial

NCT04225598 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 20000261642UG1DA015831-19
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 35

Brief 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 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.

Conditions

Opioid-use Disorder

Keywords

Opioid-use Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  7 days post randomization

Secondary Outcomes (12)

• RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization

  7 days post randomization

• RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization

  30 days post randomization

• RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization

  30 days post randomization

• RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization

  7 days post randomization

• RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization

  30 days post randomization

Other Outcomes (6)

• RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Engagement

  7 days post randomization

• RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): QALYs

  7 days post randomization

• RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Abstinent Years

  7 days post randomization

Study Arms (2)

XR-BUP

EXPERIMENTAL

Injectable buprenorphine

Drug: CAM2038

Standard SL-BUP

ACTIVE COMPARATOR

Sublingual buprenorphine

Drug: Buprenorphine Sublingual Product

Interventions

CAM2038 DRUG

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

XR-BUP

Buprenorphine Sublingual Product 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.

Standard SL-BUP

Eligibility Criteria

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

You may qualify if:

• 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.)

You may not qualify if:

• 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)
• 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:
• Be 18 years or older
• Treated in the ED during study screening hours

Sponsors & Collaborators

• Yale University: lead
• National Drug Abuse Treatment Clinical Trials Network: collaborator
• The Emmes Company, LLC: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• University of Pennsylvania: collaborator
• NYU Langone Health: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Alameda Health System: collaborator
• Weill Medical College of Cornell University: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (35)

Highland Hospital

Oakland, California, 94602, United States

Location

San Leandro Hospital

San Leandro, California, 94578, United States

Location

Yale New Haven Health (Yale New Haven Hospital)

New Haven, Connecticut, 06510, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Presybterian Hospital, Albuquerque, NM

Albuquerque, New Mexico, 87106, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

Bellevue Hospital

New York, New York, 10016, United States

Location

Icahn School of Medicine

New York, New York, 10029, United States

Location

Columbia University Irving Medical Center- NY Presbyterian

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27101, United States

Location

Pennsylvania Presbyterian Medical Center/Hospital of UPENN

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University Hospital - Episcopal Campus

Philadelphia, Pennsylvania, 19125, United States

Location

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

Rhode Island Hospital/The Miriam Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

University of Washington Medical Center- Harborview/Montlake

Seattle, Washington, 98195, United States

Location

West Virginia University - Berkeley Medical Center

Martinsburg, West Virginia, 25401, United States

Location

Related Publications (2)

• 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.

  PMID: 38976265 DERIVED

• 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.

  PMID: 36400184 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine

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

Study Officials

• Gail D'Onofrio, MD, MS

  Yale School of Medicine, Department of Emergency Medicine

  PRINCIPAL INVESTIGATOR

• David Fiellin, MD

  Yale School of Medicine, Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 13, 2020
• Study Start: July 8, 2020
• Primary Completion: December 6, 2024
• Study Completion: December 6, 2024
• Last Updated: January 10, 2025

Record last verified: 2025-01

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.

Locations

US (35)