EXHIT ENTRE Comparative Effectiveness Trial

Substance Use Disorder Clinical Trial

— EXHITENTRE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04345718
• Other study ID #: NIDA CTN 0098A
• Secondary ID: 5UG1DA040316-05
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 9, 2021
• Est. completion date: March 2026

Study information

• Verified date: February 2024
• Source: Hennepin Healthcare Research Institute
• Contact: Paulette A Baukol
• Phone: 612-873-6993
• Email: pbaukol[@]bermancenter.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 342
• Est. completion date: March 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Opioid Use Disorder, Moderate
• Opioid Use Disorder, Severe
• Opioid-Related Disorders
• Substance Use Disorder
• Substance-Related Disorders

Intervention

Drug:
• 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).
• Treatment as Usual
Community standard medication for opioid use disorder (e.g., methadone, sublingual buprenorphine, naltrexone) initiated prior to hospital discharge.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Boston University	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Hennepin Healthcare Research Institute	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Hennepin Healthcare Research Institute	National Institute on Drug Abuse (NIDA), The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of participants that experience Adverse Events (AE)	34-days following hospital discharge	34 days
Secondary	Proportion of participants engaged with MOUD	90- and 180-days following hospital discharge	Days 90 and 180 post hospital discharge
Secondary	Proportion of participants with positive urine drug test	for illicit opioids 34-, and 90-, and 180-days following hospital discharge	Days 34, 90 and 180 post hospital discharge
Secondary	Proportion of participants with self-reported opioid use		Days 34, 90 and 180 post hospital discharge
Secondary	Self-reported 30- and 90-day hospital readmission rates		Days 30 and 90 post hospital discharge
Secondary	Self-reported 30- and 90-day Emergency Department (ED) visit rates		Days 30 and 90 post hospital discharge