EXHIT ENTRE Comparative Effectiveness Trial

NCT ID: NCT04345718

Last Updated: 2025-12-09

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/PHASE3

Total Enrollment

344 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-09

Study Completion Date

2025-08-27

Brief Summary

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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.

Detailed Description

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The study will randomize approximately 314 hospitalized men and women ages 18 years and older with opioid use disorder (OUD) moderate or severe and who have not been taking prescribed medication for OUD (MOUD) for 14 days or more prior to hospitalization. Eligibility will be determined over one or more assessments during the index hospitalization. Once eligibility has been determined, participants will be randomized 1:1 to either a single injection of extended-release buprenorphine or TAU, which will include methadone, sublingual buprenorphine, or naltrexone. Connection to OUD care and ongoing MOUD following hospitalization will be per community standard. Participants will be assessed for engagement in OUD treatment by the presence of a legitimately prescribed MOUD on day 34 following hospital discharge. Further outcomes will be assessed at 90 and 180 days following hospital discharge.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Interventional

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

Group Type EXPERIMENTAL

Extended Release Buprenorphine

Intervention Type 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).

Treatment as Usual

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

Group Type ACTIVE_COMPARATOR

Treatment as Usual

Intervention Type DRUG

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

Interventions

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Extended Release Buprenorphine

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).

Intervention Type DRUG

Treatment as Usual

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

Intervention Type DRUG

Other Intervention Names

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Medication for Opioid Use Disorder Standard Medication for Opioid Use Disorder

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Anticipated length of stay less than 24-hours as determined by the ACS
2. 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:

1. Disabling terminal diagnosis for which discharge from hospital is not anticipated.
2. Disabling terminal diagnosis for which hospice care is being sought.
3. Severe alcohol or benzodiazepine use disorder that is anticipated to require complex medical detoxification which cannot be completed prior to randomization.
3. 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.
4. Liver enzyme tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT)) more than 5 times upper limit of normal or chronic decompensated liver disease.
5. Currently pregnant.
6. Known allergy to buprenorphine or components of Atrigel delivery system.
7. 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.
8. 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.
9. Previously randomized as a participant in the study - individuals may only be enrolled and randomized once.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hennepin Healthcare Research Institute

OTHER

Sponsor Role collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

Gavin Bart

OTHER

Sponsor Role lead

Responsible Party

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Gavin Bart

Gavin Bart, MD PhD FACP DFASAM

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Gavin Bart, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Hennepin Healthcare

Locations

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Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston University

Boston, Massachusetts, United States

Site Status

Hennepin Healthcare Research Institute

Minneapolis, Minnesota, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 25090173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29799968 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28673521 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39623502 (View on PubMed)

Other Identifiers

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5UG1DA040316-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIDA CTN 0098A

Identifier Type: -

Identifier Source: org_study_id

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