EXHIT ENTRE Comparative Effectiveness Trial

NCT04345718 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: NIDA CTN 0098A5UG1DA040316-05
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 6

Brief Summary

This study is a multi-site open-label randomized comparative effectiveness trial of a 28-day formulation of extended-release buprenorphine (XR-BUP) versus treatment as usual (TAU) for hospitalized patients with a moderate or severe opioid use disorder (OUD) seen by an addiction consultation service (ACS) and agreeing to initiate a medication for OUD (MOUD). Participants will be randomly assigned to XR-BUP or TAU to be received within 72 hours of anticipated hospital discharge. Follow up will occur at approximately 34, 90, and 180 days following hospital discharge.

Conditions

Opioid Use Disorder, Moderate; Opioid Use Disorder, Severe; Substance Use Disorder

Keywords

MOUD; XR-BUP; ACS; OUD; SUD

Outcome Measures

Primary Outcomes (1)

• The proportion of participants engaged in OUD care on the 34th day following hospital discharge.

  Engagement in OUD is defined as coverage with a legitimately prescribed MOUD on that 34th day regardless of the source of prescribed MOUD coverage (e.g., formalized treatment program, primary care, jail, etc.).

  34 days post discharge from hospital

Secondary Outcomes (6)

• Proportion of participants that experience Adverse Events (AE)

  34 days

• Proportion of participants engaged with MOUD

  Days 90 and 180 post hospital discharge

• Proportion of participants with positive urine drug test

  Days 34, 90 and 180 post hospital discharge

• Proportion of participants with self-reported opioid use

  Days 34, 90 and 180 post hospital discharge

• Self-reported 30- and 90-day hospital readmission rates

  Days 30 and 90 post hospital discharge

Study Arms (2)

Interventional

EXPERIMENTAL

Single subcutaneous injection of a 28-day formulation of extended-release buprenorphine within 72 hours of anticipated hospital discharge.

Drug: Extended Release Buprenorphine

Treatment as Usual

ACTIVE COMPARATOR

Community standard of care that includes initiation of either methadone, sublingual (SL) buprenorphine, or naltrexone prior to hospital discharge.

Drug: Treatment as Usual

Interventions

Extended Release Buprenorphine DRUG

XR-BUP administration prior to hospital discharge will increase engagement in OUD care on the 34th day following hospital discharge more than is currently afforded by ACS TAU approaches (e.g., methadone, SL-BUP, and naltrexone).

Also known as: Medication for Opioid Use Disorder

Interventional

Treatment as Usual DRUG

Community standard medication for opioid use disorder (e.g., methadone, sublingual buprenorphine, naltrexone) initiated prior to hospital discharge.

Also known as: Standard Medication for Opioid Use Disorder

Treatment as Usual

Eligibility Criteria

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

You may qualify if:

• Hospitalized.
• At least 18 years of age.
• Meet Diagnostic and Statistical Manual (DSM-5) criteria for moderate or severe OUD.
• Willing to initiate MOUD, including buprenorphine.
• Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.

You may not qualify if:

• Anticipated length of stay less than 24-hours as determined by the ACS
• Affected by a serious medical, psychiatric, or substance use disorder that, in the opinion of the study physician, would make it unsafe to participate in the study or may prevent collection of study data. This may include:
• Disabling terminal diagnosis for which discharge from hospital is not anticipated.
• Disabling terminal diagnosis for which hospice care is being sought.
• Severe alcohol or benzodiazepine use disorder that is anticipated to require complex medical detoxification which cannot be completed prior to randomization.
• Taking a long-acting opioid other than buprenorphine (e.g., methadone, extended-release oxycodone, extended-release morphine) in the three consecutive days prior to randomization.
• Liver enzyme tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT)) more than 5 times upper limit of normal or chronic decompensated liver disease.
• Currently pregnant.
• Known allergy to buprenorphine or components of Atrigel delivery system.
• Receipt of MOUD in the 14 days prior to hospitalization as maintenance treatment; however, patients may have received MOUD for withdrawal management during or prior to hospitalization at the time of enrollment.
• Are currently in jail, prison or other overnight facility as required by court of law and/or is considered a prisoner under local law or is under current terms of civil commitment or guardianship.
• Previously randomized as a participant in the study - individuals may only be enrolled and randomized once.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• The Emmes Company, LLC: collaborator
• Gavin Bart: lead
• Hennepin Healthcare Research Institute: collaborator

Study Sites (6)

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Hennepin Healthcare Research Institute

Minneapolis, Minnesota, 55404, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (4)

• Liebschutz JM, Crooks D, Herman D, Anderson B, Tsui J, Meshesha LZ, Dossabhoy S, Stein M. Buprenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. JAMA Intern Med. 2014 Aug;174(8):1369-76. doi: 10.1001/jamainternmed.2014.2556.

  PMID: 25090173 BACKGROUND

• Lofwall MR, Walsh SL, Nunes EV, Bailey GL, Sigmon SC, Kampman KM, Frost M, Tiberg F, Linden M, Sheldon B, Oosman S, Peterson S, Chen M, Kim S. Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Intern Med. 2018 Jun 1;178(6):764-773. doi: 10.1001/jamainternmed.2018.1052.

  PMID: 29799968 BACKGROUND

• Trowbridge P, Weinstein ZM, Kerensky T, Roy P, Regan D, Samet JH, Walley AY. Addiction consultation services - Linking hospitalized patients to outpatient addiction treatment. J Subst Abuse Treat. 2017 Aug;79:1-5. doi: 10.1016/j.jsat.2017.05.007. Epub 2017 May 11.

  PMID: 28673521 BACKGROUND

• Bart G, Barth KS, Baukol P, Enns E, Ghitza UE, Harris J, Jelstrom E, Liebschutz JM, Magane KM, Voronca D, Weinstein ZM, Korthuis PT. Exemplar Hospital Initiation Trial to Enhance Treatment Engagement (EXHIT ENTRE): protocol for CTN-0098 an open-label randomized comparative effectiveness trial of extended-release buprenorphine versus treatment as usual on post-hospital treatment engagement for hospitalized patients with opioid use disorder. Addict Sci Clin Pract. 2024 Dec 2;19(1):91. doi: 10.1186/s13722-024-00510-5.

  PMID: 39623502 DERIVED

MeSH Terms

Conditions

Substance-Related Disorders; Opioid-Related Disorders; Lymphoma, Follicular

Interventions

Dosage Forms; Therapeutics

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Gavin Bart, MD,PhD

  Hennepin Healthcare

  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 INVESTIGATOR
• PI Title: Gavin Bart, MD PhD FACP DFASAM

Model Details: This is a multi-site open-label randomized comparative effectiveness trial of a 28-day formulation of XR-BUP versus TAU for hospitalized patients with OUD agreeing to MOUD. Approximately 4-5 sites (hospitals) with existing ACSs experienced in hospital-initiated MOUD will be selected. Identification of patients with OUD will occur as per each site's local practice. Approximately 314 hospitalized patients with OUD who were not receiving prescribed MOUD for at least 14 days prior to hospitalization and are willing to start MOUD including buprenorphine will be randomized 1:1 to two different strategies. After baseline assessments are performed, eligible participants will be randomized in a 1:1 ratio to XR-BUP or TAU

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: August 9, 2021
• Primary Completion: August 27, 2025
• Study Completion: August 27, 2025
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be shared after the primary outcome paper has been accepted for publication, or 18 months after data lock, whichever comes first. The data will remain indefinitely.
• Access Criteria: Data from this study will be available to researchers on the website https://datashare.nida.nih.gov/ after the study is complete and the data is analyzed. This website will not include information that can identify individual study participants.The following information will be posted: Study protocol, reference to study publication of primary outcome, data sets (SAS and ASCII ), annotated case report forms, define file (also known as Data Dictionary), study-specific de-identification notes. Prior to downloading any study data, the user will be prompted to complete a registration agreement for data use. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the NIDA Data Share Agreement.

Locations

US (6)