Clinical trial NCT04225598: Emergency Department-Initiated Buprenorphine Validation Network Trial
Official title: Emergency Department-Initiated Buprenorphine Validation Network Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-use Disorder
Keywords: Opioid-use Disorder
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Drug Abuse Treatment Clinical Trials Network
name: The Emmes Company, LLC
name: Harvard Medical School (HMS and HSDM)
name: University of Pennsylvania
name: NYU Langone Health
name: Icahn School of Medicine at Mount Sinai
name: Alameda Health System
name: Weill Medical College of Cornell University
name: National Institute on Drug Abuse (NIDA)
First posted: 2020-01-13
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will (1) recruit, train and provide resources to approximately 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to provide ED-initiated buprenorphine (BUP) for patients presenting with opioid use disorder (OUD) who are not receiving medications for opioid use disorder (MOUD). Once implementation is adequately achieved, the sites will (2) conduct a randomized controlled trial (RCT) to compare the effectiveness of sublingual buprenorphine (SL-BUP) versus extended-release buprenorphine (XR-BUP) on ED patients' engagement in formal addiction treatment 7-days after their ED visit. In addition, in an ancillary component of the study, the investigators will (3) assess the use of XR-BUP in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores \< 8 in a case series to potentially expand the eligibility of patients in the larger RCT to those presenting with little to no opioid withdrawal symptoms. Finally, the investigators will (4) develop and validate ED electronic health record (EHR) opioid-related phenotypes, both of which will inform the main RCT.

Detailed description: The study will be comprised of four components as outlined below:

1. Site implementation component:

   In this component, the investigators will use previously developed implementation facilitation strategies and resources to train ED providers and staff at approximately 30 diverse EDs in treatment initiation with SL-BUP and XR-BUP and develop ED buprenorphine protocols and procedures. The investigators anticipate that this will result in a minimum of 24 sites (80%) that will meet the implementation milestones for competence in ED-initiated BUP using standard SL and XR-BUP inductions.
2. Effectiveness RCT component:

   This component is a large pragmatic RCT using a Hybrid Type 1 Effectiveness-Implementation design. Sites that satisfactorily complete the site implementation component will be activated on a rolling basis for the RCT after demonstrated implementation milestones have been met. In this Hybrid Type 1 design the primary research question is the effectiveness of SL-BUP induction compared with that of XR-BUP on the primary outcome measure of engagement in formal addiction treatment at 7-days post ED visit. This design also allows us to gather information and report on implementation processes.
3. Ancillary component - XR-BUP Induction for patients with COWS \< 8:

   This observational case series will begin in advance of the Effectiveness RCT component at approximately 4 ED sites with extensive experience in ED-initiated BUP. The investigators will collect quantitative and qualitative data on the use of XR-BUP in ED patients with low COWS scores for approximately 75 patients. Sites will receive a supply of XR-BUP for provision to up to 5 patients with a COWS score \> 8. The purpose is to pre-study the procedures at the four ancillary study sites on treating OUD patients with XR-BUP prior to initiation of the ancillary component. Data collected from this pre-study will not be included in the analysis of the ancillary and effectiveness RCT component. These initial up to 20 pre-study patients will meet all other study criteria and undergo all assessments. It is anticipated that the information collected from the 75 patients in the ancillary component will allow for modification to the larger Effectiveness RCT by expanding eligibility criteria to include patients with COWS \<8.
4. Development and validation of EHR ED opioid-related phenotypes component:

   In this component, the investigators will develop EHR phenotypes of opioid-related illnesses that accurately and automatically characterize patient conditions, enhance the ability to actively monitor and surveil, and better identify representative samples and patients potentially eligible for study inclusion, leading ultimately to an enhanced inclusion and understanding of opioid-related conditions. At the primary Yale New Haven Health System sites, the phenotypes (rules- and machine learning-based) will be iteratively developed and internally validated. The rules-based phenotype will be mapped to a common data model and externally validated at 4 trial sites.
5. An exploratory outcome of this study will be to assess the impact of COVID-19 on ED use for opioid-related diagnoses using EHR data.

The primary focus of this clinicaltrials.gov registration are the RCT outcomes. Implementation and ancillary outcomes will be identified as secondary outcomes for the purpose of this clinicaltrials.gov registration

Eligibility criteria: RCT Component:

Inclusion Criteria:

1. Be 18 years or older
2. Treated in the ED during study screening hours
3. Meet DSM-5 (Diagnostic and Statistical Manual) diagnostic criteria for moderate to severe OUD
4. Have a COWS score of \> or equal to 4
5. Have a urine toxicology test that is positive for opioids (opiates, oxycodone, buprenorphine). Patients with urines that are only positive for fentanyl will be eligible if their clinical history and physical exam are consistent with opioid use and they meet DSM-5 criteria for moderate to severe OUD.
6. Able to speak English sufficiently to understand the study the study procedures and provide written informed consent to participate in the study. (Exception may be made if sites with large population of Spanish speaking patients are accepted for participation in the study and study materials are translated into Spanish. Translated study materials will be reviewed and approved by the Institutional Review Board) IRB of record prior to use.)

Exclusion Criteria:

1. Have urine toxicology test that is positive for methadone
2. Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
3. Have a medical or psychiatric condition that requires hospitalization
4. Opioid administration (excluding BUP) at the index ED visit, prior to enrollment, and COWS remains \< 8 during ED stay
5. Be actively suicidal or severely cognitively impaired precluding informed consent
6. Present from an extended care facility (e.g., skilled nursing facility)
7. Require continued prescription opioids for a pain condition
8. Be a prisoner or in police custody at the time of index ED visit
9. Be currently (anytime within the past 14 days) enrolled in formal addiction treatment, including by court order. Patients enrolled in formal addiction who are not receiving MOUD are eligible
10. Be unable to provide reliable locator information including 2 contact numbers in addition to their own
11. Be unwilling to follow study procedures (e.g., unwilling to provide permission to contact referral provider/program or unavailable for the follow-up assessments)
12. Have prior enrollment in the current study component

Ancillary Component:

Inclusion Criteria:

1. Be 18 years or older
2. Treated in the ED during study screening hours
3. Meet DSM-5 diagnostic criteria for moderate to severe opioid use disorder
4. Have a COWS \<8
5. Have a urine toxicology test that is positive for opioids (opiates, oxycodone, or buprenorphine). Patients with urines that are only positive for fentanyl on the point of care test strip will be eligible if their clinical history and physical exam are consistent with opioid use and they meet DSM-5 criteria for moderate to severe OUD.
6. Be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study

Exclusion Criteria:

1. Have a urine toxicology test that is positive for methadone
2. Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
3. Have a medical or psychiatric condition that requires hospitalization at the index ED visit, prior to enrollment
4. Be actively suicidal or severely cognitively impaired precluding informed consent
5. Present from an extended care facility (e.g., skilled nursing facility)
6. Require continued prescription opioids for a pain condition
7. Be a prisoner or in police custody at the time of index ED visit
8. Be currently (anytime within the past 7 days) enrolled in formal addiction treatment, including by court order. Patients enrolled in formal addiction treatment but are not receiving MOUD are eligible
9. Be unable to provide reliable locator information including 2 contact numbers in addition to their own
10. Be unwilling to follow study procedures (e.g., unwilling to provide permission to answer daily assessments until day 7)
11. Have prior enrollment in the current study

Primary outcomes:
measure: RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization
timeFrame: 7 days post randomization
Secondary outcomes:
measure: RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization
timeFrame: 7 days post randomization
measure: RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization
timeFrame: 30 days post randomization
measure: RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization
timeFrame: 30 days post randomization
measure: RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization
timeFrame: 7 days post randomization
measure: RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization
timeFrame: 30 days post randomization
measure: RCT Component: Craving scores at 7 days post randomization
timeFrame: 7 days post randomization
measure: RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization
timeFrame: 30 days post randomization
measure: RCT Component: Patient satisfaction with BUP at 7 days post randomization
timeFrame: 7 days post randomization
measure: RCT Component: Overdose Events at 30 days post randomization
timeFrame: 30 days post randomization
measure: Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration
timeFrame: Within 4 hours of XR-BUP administration
measure: Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration
timeFrame: Within 4 hours of XR-BUP administration
measure: Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration
timeFrame: Within 1 hour post XR-BUP injection
Other outcomes:
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Engagement
timeFrame: 7 days post randomization
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): QALYs
timeFrame: 7 days post randomization
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Abstinent Years
timeFrame: 7 days post randomization
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Engagement
timeFrame: 30 days post randomization
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): QALYs
timeFrame: 30 days post randomization
measure: RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Abstinent Years
timeFrame: 30 days post randomization
Locations:
city: Oakland
country: United States
facility: Highland Hospital
state: California
city: San Leandro
country: United States
facility: San Leandro Hospital
state: California
city: New Haven
country: United States
facility: Yale New Haven Health (Yale New Haven Hospital)
state: Connecticut
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: Presybterian Hospital, Albuquerque, NM
state: New Mexico
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: New York
country: United States
facility: Bellevue Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center- NY Presbyterian
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Syracuse
country: United States
facility: Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Philadelphia
country: United States
facility: Pennsylvania Presbyterian Medical Center/Hospital of UPENN
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital - Episcopal Campus
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Mercy Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital/The Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Seattle
country: United States
facility: University of Washington Medical Center- Harborview/Montlake
state: Washington
city: Martinsburg
country: United States
facility: West Virginia University - Berkeley Medical Center
state: West Virginia
Study officials:
affiliation: Yale School of Medicine, Department of Emergency Medicine
name: Gail D'Onofrio, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale School of Medicine, Department of Internal Medicine
name: David Fiellin, MD
role: PRINCIPAL_INVESTIGATOR
References: