Substance Use DisorderPhase 2/3EXHITENTRENCT04345718
EXHIT ENTRE Comparative Effectiveness Trial
A Phase 2/3 study testing Extended Release Buprenorphine and Treatment as Usual in people with Substance Use Disorder and Opioid Use Disorder, Moderate, run by Gavin Bart at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Substance Use Disorder, Opioid Use Disorder, Moderate, Opioid Use Disorder, Severe
- What is being tested?
- Extended Release Buprenorphine and Treatment as Usual
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 344 participants
- Where
- 6 sitesUnited States
- Study dates
- 9 Aug 2021to 27 Aug 2025
- Phase
- Phase 2/3
- 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
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston University
Boston, Massachusetts, 02118
Hennepin Healthcare Research Institute
Minneapolis, Minnesota, 55404
Yale New Haven Hospital
New Haven, Connecticut, 06520
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Exemplar Hospital Initiation Trial to Enhance Treatment Engagement - Comparative Effectiveness Trial of Extended Release Buprenorphine Versus Treatment as Usual for Hospitalized Patients With Opioid Use Disorder
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.
Read the detailed description
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.
- Being tested
- Extended Release Buprenorphine, Treatment as Usual
- Keywords
- MOUD, XR-BUP, ACS, OUD, SUD
- Medical subject headings
- Substance-Related Disorders, Opioid-Related Disorders, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended Release BuprenorphineDrug
Also called Medication for Opioid Use Disorder
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 called Standard Medication for Opioid Use Disorder
Community standard medication for opioid use disorder (e.g., methadone, sublingual buprenorphine, naltrexone) initiated prior to hospital discharge.
| Study group | Role | What they receive |
|---|---|---|
| Interventional | Experimental | Single subcutaneous injection of a 28-day formulation of extended-release buprenorphine within 72 hours of anticipated hospital discharge. Receives: 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. Receives: Drug: Treatment as Usual |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.).
Measured: 34 days post discharge from hospital
Secondary outcomes (6)
Proportion of participants that experience Adverse Events (AE)
34-days following hospital discharge
Measured: 34 days
Proportion of participants engaged with MOUD
90- and 180-days following hospital discharge
Measured: Days 90 and 180 post hospital discharge
Proportion of participants with positive urine drug test
for illicit opioids 34-, and 90-, and 180-days following hospital discharge
Measured: Days 34, 90 and 180 post hospital discharge
Proportion of participants with self-reported opioid use
Measured: Days 34, 90 and 180 post hospital discharge
Self-reported 30- and 90-day hospital readmission rates
Measured: Days 30 and 90 post hospital discharge
Self-reported 30- and 90-day Emergency Department (ED) visit rates
Measured: Days 30 and 90 post hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2020
- Study start9 Aug 2021
- Primary completion27 Aug 2025
- Study completion27 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Substance Use DisorderStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 344 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gavin Bart
- Sponsor type
- University, hospital or other
- Collaborators
- Hennepin Healthcare Research Institute, National Institute on Drug Abuse (NIDA), The Emmes Company, LLC
- Responsible party
- Sponsor-investigator, Gavin Bart, Hennepin Healthcare Research Institute
- Investigators
- Gavin Bart, MD,PhD, Principal investigator, Hennepin Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04345718
- Sponsor's protocol ID
- NIDA CTN 0098A
- Other IDs
- 5UG1DA040316-05
- Acronym
- EXHITENTRE
- Status last verified
- Dec 2025
- First submitted
- 9 Apr 2020
- Last updated
- 9 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be transmitted by the study Data and Statistics Center to the designated party for de-identification, posting, storing, and archiving on the National Institute on Drug Abuse (NIDA) Data Share website. Data Share is an online repository of data from studies funded by the National Institute on Drug Abuse. De-identified individual participant data is expected to be made available.
Publications
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.
PubMed 25090173Lofwall 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.
PubMed 29799968Trowbridge 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.
PubMed 28673521Bart 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.
PubMed 39623502
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exemplar Hospital Initiation Trial to Enhance Treatment Engagement - Comparative Effectiveness Trial of Extended Release Buprenorphine Versus Treatment as Usual for Hospitalized Patients With Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT04345718
- Acronym / sponsor ID
- EXHITENTRE / NIDA CTN 0098A
- Keywords
- MOUD, XR-BUP, ACS, OUD, SUD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 344 participants (actual)
- Lead sponsor
- Gavin BartUniversity, hospital or other
- Collaborators
- Hennepin Healthcare Research Institute, National Institute on Drug Abuse (NIDA), The Emmes Company, LLC
- Study start
- 9 Aug 2021 (actual)
- Primary completion
- 27 Aug 2025 (actual)
- Study completion
- 27 Aug 2025 (actual)
- First posted
- 14 Apr 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 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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Interventional | Experimental | Drug: Extended Release BuprenorphineSingle subcutaneous injection of a 28-day formulation of extended-release buprenorphine within 72 hours of anticipated hospital discharge. |
| Treatment as Usual | Active comparator | Drug: Treatment as UsualCommunity standard of care that includes initiation of either methadone, sublingual (SL) buprenorphine, or naltrexone prior to hospital discharge. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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:
- 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.
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 |
|---|---|---|
| Extended Release BuprenorphineAlso: Medication for Opioid Use DisorderXR-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). | Drug | Interventional |
| Treatment as UsualAlso: Standard Medication for Opioid Use DisorderCommunity standard medication for opioid use disorder (e.g., methadone, sublingual buprenorphine, naltrexone) initiated prior to hospital discharge. | Drug | Treatment as Usual |
Primary outcome
The proportion of participants engaged in OUD care on the 34th day following hospital discharge.
Time frame: 34 days post discharge from hospital
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.).
6 secondary outcomes
Proportion of participants that experience Adverse Events (AE)
Time frame: 34 days
Proportion of participants engaged with MOUD
Time frame: Days 90 and 180 post hospital discharge
Proportion of participants with positive urine drug test
Time frame: Days 34, 90 and 180 post hospital discharge
Proportion of participants with self-reported opioid use
Time frame: Days 34, 90 and 180 post hospital discharge
Self-reported 30- and 90-day hospital readmission rates
Time frame: Days 30 and 90 post hospital discharge
Self-reported 30- and 90-day Emergency Department (ED) visit rates
Time frame: Days 30 and 90 post hospital discharge
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 9 Dec 2025.
- Background: PubMed 25090173Liebschutz 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.
- Background: PubMed 29799968Lofwall 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.
- Background: PubMed 28673521Trowbridge 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.
- Derived from this study: PubMed 39623502Bart 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.
- Individual participant dataSharing planned: Yes. Data will be transmitted by the study Data and Statistics Center to the designated party for de-identification, posting, storing, and archiving on the National Institute on Drug Abuse (NIDA) Data Share website. Data Share is an online repository of data from studies funded by the National Institute on Drug Abuse. De-identified individual participant data is expected to be made available.
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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.
Gavin Bart, MD,PhD principal investigator
Hennepin Healthcare
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Extended Release Buprenorphine and Treatment as Usual in people with Substance Use Disorder and Opioid Use Disorder, Moderate, run by Gavin Bart at 6 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 5 inclusion and 12 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 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
The proportion of participants engaged in OUD care on the 34th day following hospital discharge. (time frame: 34 days post discharge from hospital). 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 NCT04345718, which also lists 4 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 9 Dec 2025.