Clinical trial NCT04345718: EXHIT ENTRE Comparative Effectiveness Trial
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Substance Use Disorder
Opioid Use Disorder, Moderate
Opioid Use Disorder, Severe
Keywords: MOUD
XR-BUP
ACS
OUD
SUD
Lead sponsor: Hennepin Healthcare Research Institute
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: The Emmes Company, LLC
First posted: 2020-04-14
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of participants engaged in OUD care on the 34th day following hospital discharge.
timeFrame: 34 days post discharge from hospital
Secondary outcomes:
measure: Proportion of participants that experience Adverse Events (AE)
timeFrame: 34 days
measure: Proportion of participants engaged with MOUD
timeFrame: Days 90 and 180 post hospital discharge
measure: Proportion of participants with positive urine drug test
timeFrame: Days 34, 90 and 180 post hospital discharge
measure: Proportion of participants with self-reported opioid use
timeFrame: Days 34, 90 and 180 post hospital discharge
measure: Self-reported 30- and 90-day hospital readmission rates
timeFrame: Days 30 and 90 post hospital discharge
measure: Self-reported 30- and 90-day Emergency Department (ED) visit rates
timeFrame: Days 30 and 90 post hospital discharge
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Healthcare Research Institute
state: Minnesota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Hennepin Heatlhcare
name: Gavin Bart, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.