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Emergency Department-Initiated Buprenorphine Validation Network Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04225598
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : September 8, 2021
Sponsor:
Collaborators:
National Drug Abuse Treatment Clinical Trials Network
The Emmes Company, LLC
Harvard Medical School (HMS and HSDM)
University of Pennsylvania
NYU Langone Health
Icahn School of Medicine at Mount Sinai
Alameda Health System
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE December 20, 2019
First Posted Date  ICMJE January 13, 2020
Last Update Posted Date September 8, 2021
Actual Study Start Date  ICMJE July 8, 2020
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2020)
  • RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization [ Time Frame: 7 days post randomization ]
    Engagement in formal addiction treatment will be defined as enrollment and receiving formal addiction treatment on the 7th day post randomization, confirmed by contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, opioid treatment programs (OTPs), intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD at 7 days to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics Anonymous (AA) or (Narcotics Anonymous) NA alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
  • RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization [ Time Frame: 30 days post randomization ]
    Engagement in formal addiction treatment will be defined as enrollment in formal addiction treatment on the 30th day post randomization, confirmed by direct contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, OTPs, intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD on the 30th day post randomization to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics or Narcotics Anonymous alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
  • RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The primary economic outcome will be the incremental cost-effectiveness ratio (ICER). The ICER will be calculated as the incremental mean cost of XR-BUP relative to SL-BUP, divided by the incremental mean effectiveness of XR-BUP relative to SL-BUP. Measures of effectiveness include: engagement in formal addiction treatment at 7 days and on the 30th day; quality-adjusted life-years (QALYs) gained; and Abstinent Years, a measure of time abstinent from opioids.
  • RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP at 30 days post randomization [ Time Frame: 30 days post randomization ]
    The primary economic outcome will be the incremental cost-effectiveness ratio (ICER). The ICER will be calculated as the incremental mean cost of XR-BUP relative to SL-BUP, divided by the incremental mean effectiveness of XR-BUP relative to SL-BUP. Measures of effectiveness include: engagement in formal addiction treatment at 7 days and on the 30th day; quality-adjusted life-years (QALYs) gained; and Abstinent Years, a measure of time abstinent from opioids.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2020)
  • RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    self-report verified with treatment provider(s)
  • RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
  • RCT Component: Self-reported days (quantity) of illicit opioid use (past 7 days) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported quantity of use of opioids.
  • RCT Component: Self-reported days (route of administration) of illicit opioid use (past 7 days) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported route of administration of use of opioids.
  • RCT Component: Craving scores at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The investigators will use visual analogue scales (VAS) to assess craving, desire to use opioids and need to use opioids with a scale of 0-100.
  • RCT Component: Patient satisfaction with BUP at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The investigators will modify the patient satisfaction scale where overall experience is rated from 1 to 5 (1 is completely ineffective and 5 is completely effective) and treatment characteristics are rated 1 to 7 (1 is not important and 7 is extremely important) based on previous published data.
  • RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    self report verified with treatment provider(s)
  • RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
  • RCT Component: Self-reported days (quantity) of illicit opioid use (past 7 days) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported quantity of use of opioids.
  • RCT Component: Self-reported days (route of administration) of illicit opioid use (past 7 days) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported route of administration of use of opioids.
  • RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization [ Time Frame: 30 days post randomization ]
    A brief, structured interview regarding health care utilization (inpatient and outpatient) will be used, which collects information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment and self-help sources of support (e.g., NA).
  • RCT Component: Overdose Events at 30 days post randomization [ Time Frame: 30 days post randomization ]
    Assessment of past 30-day overdose events will be completed at 30 days post study enrollment. In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
  • BUP Implementation Component (ED): Change in the number of ED visits during which BUP is administered in the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of ED visits during which BUP is administered in ED- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of ED visits during which BUP is administered in the ED (prior 30 days ) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of ED visits during which BUP is administered in ED- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of ED visits during which BUP is administered in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of ED visits during which BUP is administered in ED- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days ) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of ED visits during which patients receive a prescription for BUP in ED- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of ED visits during which patients receive a prescription for BUP in ED- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of ED visits during which patients receive a prescription for BUP in ED- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of unique ED prescribers who are DATA 2000 X-waivered- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who are DATA 2000 X-waivered- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who are DATA 2000 X-waivered- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of unique ED prescribers who administered BUP in ED- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who administered BUP in ED- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who administered BUP in ED- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of unique ED prescribers who prescribe BUP in ED- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who prescribe BUP in ED- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of unique ED prescribers who prescribe BUP in ED- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in percent adherence to Critical Action Checklist for ED-initiated SL-BUP and XR-BUP- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in percent adherence to Critical Action Checklist for ED-initiated SL-BUP and XR-BUP- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in percent adherence to Critical Action Checklist for ED-initiated SL-BUP and XR-BUP- 6 months post site initiation to 12 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of past 30-day change in number of ED prescribers who fully adhere to critical action checklist- Baseline to site initiation.
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of past 30-day change in number of ED prescribers who fully adhere to critical action checklist- Site initiation to 6 months post site initiation.
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of past 30-day change in number of ED prescribers who fully adhere to critical action checklist- 6 months post site initiation to 12 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of change in number of programs accepting patients into formal addiction treatment at 7 days following ED visit- Baseline to site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: Site Initiation to 6 months post site initiation ]
    Assessment of change in number of programs accepting patients into formal addiction treatment at 7 days following ED visit- Site Initiation to 6 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of change in number of programs accepting patients into formal addiction treatment at 7 days following ED visit- 6 months post site initiation to 12 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of change in number of formal systems pathways in place for arranging referrals for ongoing MOUD- Baseline to site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: Site Initiation to 6 months post site initiation ]
    Assessment of change in number of formal systems pathways in place for arranging referrals for ongoing MOUD- Site Initiation to 6 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of change in number of formal systems pathways in place for arranging referrals for ongoing MOUD- 6 months post site initiation to 12 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of change in proportion of patients engaged in formal addiction treatment at 7 days following ED visit- Baseline to site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of change in proportion of patients engaged in formal addiction treatment at 7 days following ED visit- Site initiation to 6 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of change in proportion of patients engaged in formal addiction treatment at 7 days following ED visit- 6 months post site initiation to 12 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
    Assessment of change in proportion of patients engaged in MOUD at 7 days following ED visit- Baseline to site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: Site initiation to 6 months post site initiation ]
    Assessment of change in proportion of patients engaged in MOUD at 7 days following ED visit- Site initiation to 6 months post site initiation.
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
    Assessment of change in proportion of patients engaged in MOUD at 7 days following ED visit- 6 months post site initiation to 12 months post site initiation.
  • Ancillary Component: Desire to Use post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100.
  • Ancillary Component: Bad drug effects post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post injection ]
    The investigators will use a VAS to assess bad drug effects. Participants will be asked to respond to the statement: "At this moment, I feel bad drug effects" and place a mark across the line at the point that corresponds to the extent to which they are feeling any bad drug effects. Anchors will include 0 mm - 'not at all' to 100 mm - 'extremely'.
  • Ancillary Component: Changes in withdrawal severity at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post-injection ]
    Adjective Rating Scale for Withdrawal (ARSW) - The ARSW is a 16-item self-report scale that measures subjective severity of opioid withdrawal and symptoms using a scale of 1 to 9 (1 is none and 9 is severe).
  • Ancillary Component: Pain at injection site post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Immediately following XR-BUP injection, 30 minutes and 240 minutes post injection ]
    Participants will report the degree of pain at the injection site after the injection is administered using a numerical rating scale ranging from 0 - no pain to 10 - worst possible pain.
  • Ancillary Component: Vital Signs (temperature) post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (temperature) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (blood pressure- systolic) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (systolic blood pressure, mmHg) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (diastolic blood pressure) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (diastolic blood pressure, mmHg) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (pulse rate) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (pulse rate- beats per minute) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (respiratory rate) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (respiratory rate- breaths/min) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (oxygen saturation) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (oxygen saturation- collected while sitting, following a rest period of at least 3 minutes) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Changes in withdrawal severity (COWS) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Changes in withdrawal severity (OOWS) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    The Objective Opioid Withdrawal Scale (OOWS) - The OOWS is a validated measure of the severity of opioid withdrawal that consists of 13 objective items.
  • Ancillary Component: Changes in withdrawal severity (ARSW) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Adjective Rating Scale for Withdrawal (ARSW) - The ARSW is a 16-item self-report scale that measures subjective severity of opioid withdrawal and symptoms using a scale of 1 to 9 (1 is none and 9 is severe).
  • Ancillary Component: Pupillary diameter post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    This will be assessed via pupillometry. Two measurements should be taken and if they are discrepant by >0.5mm discrepant, the Research Associate will need to repeat assessment until they achieve two consecutive readings with agreement of <0.5mm. The average of the two measurements is entered.
  • Ancillary Component: Provision of post Injection Medications post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    SL-BUP and ancillary medications will be provided according to a uniform protocol. Research Associates (RAs) and nurses will document the timing and provision of all medications received before and during the 4-hour observation period in the ED. In addition, the Research Associate will review the electronic medical record to determine any additional medications or intravenous fluids were administered to the patient during their ED visit and the timing of those medications.
  • Ancillary Component: Precipitated Withdrawal (yes/no) post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Precipitated Withdrawal will be documented on the Precipitated Withdrawal Form along with time of occurrence.
  • Ancillary Component: Local Tolerability post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: At 30 and 240 minutes post XR-BUP injection ]
    The Research Associate will assess the degree of erythema and swelling at the injection site using a 4-point rating scale ranging from 0 - none to 3-severe.
  • Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration [ Time Frame: Within 1 hour post XR-BUP injection ]
    Assessment of Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration.
  • Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration [ Time Frame: Within 4 hours of XR-BUP administration ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration [ Time Frame: Within 4 hours of XR-BUP administration ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Daily Substance Use (Days 1-6 post injection) [ Time Frame: Days 1-6 post injection ]
    The Daily Substance Use assessment solicits participant use of substances of interest daily via a text-messaging application.
  • Ancillary Component: Desire to Use (Days 1-6 post injection) [ Time Frame: Days 1-6 post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100 (daily via a text-messaging application).
  • Ancillary Component: Presence of opioids, oxycodone, benzodiazepines, cocaine, methamphetamine, amphetamine, ecstasy (MDMA), marijuana (THC), barbiturate, methadone, buprenorphine and fentanyl (7 days post injection) [ Time Frame: 7 days post injection ]
    Urine testing will be performed for the presence of the following drugs: opioids, oxycodone, benzodiazepines, cocaine, methamphetamine, amphetamine, ecstasy (MDMA), marijuana (THC), barbiturate, methadone, buprenorphine, and fentanyl.
  • Ancillary Component: Opioid Withdrawal (7 days post injection) [ Time Frame: 7 days post injection ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Daily Substance Use (7 days post injection) [ Time Frame: 7 days post injection ]
    The Daily Substance Use assessment solicits participant use of substances of interest.
  • Ancillary Component: Desire to Use (7 days post injection) [ Time Frame: 7 days post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100
  • Ancillary Component: Injection Site Reactions (7 days post injection) [ Time Frame: 7 days post injection ]
    At 7-day follow up the participant will be queried about pain, itching, discharge and tenderness at the site. Study staff will examine the patient for erythema at the injection.
  • Ancillary Component: Patient satisfaction with BUP (7 days post injection) [ Time Frame: 7 days post injection ]
    Participant satisfaction and preference will be assessed using quantitative and qualitative mixed methods at 7-day follow-up. Satisfaction will be rated on a Likert 1-5 scale by the participant, and preference order ranking to receive ongoing treatment with SL-BUP, preference to receive ongoing treatment with XR-BUP, and preference to not receive any formulation of BUP will be ranked. The investigators will use open-ended questions to explore patient satisfaction, preference and study experience.
  • Ancillary Component: Health Services Utilization (7 days post injection) [ Time Frame: 7 days post injection ]
    A brief, structured interview (not scored) regarding health care utilization (inpatient and outpatient) will be used, which collects information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment and self-help sources of support (e.g., NA).
  • Ancillary Component: Engagement in Treatment (7 days post injection) [ Time Frame: 7 days post injection ]
    At 7 days post enrollment, participants will be asked to report OUD treatment received. Data will be reported on the Engagement in Treatment - Patient Survey (not scored).
  • Ancillary Component: Overdose Events (7 days post injection) [ Time Frame: 7 days post injection ]
    Assessment of past 30-day overdose events will be completed at day 7 In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2020)
  • RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    self-report verified with treatment provider(s)
  • RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids, marijuana, stimulants, benzodiazepines and alcohol. On days of reported use the following information will be collected: quantity and route of administration.
  • RCT Component: Craving scores at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The investigators will use visual analogue scales (VAS) to assess craving, desire to use opioids and need to use opioids with a scale of 0-100.
  • RCT Component: Patient satisfaction with BUP at 7 days post randomization [ Time Frame: 7 days post randomization ]
    The investigators will modify the patient satisfaction scale where overall experience is rated from 1 to 5 (1 is completely ineffective and 5 is completely effective) and treatment characteristics are rated 1 to 7 (1 is not important and 7 is extremely important) based on previous published data.
  • RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    self report verified with treatment provider(s)
  • RCT Component: Self-reported use of illicit opioid use (past 7 days) at 30 days post randomization [ Time Frame: 30 days post randomization ]
    The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported use, quantity, and route of administration of opioids, marijuana, stimulants, benzodiazepines and alcohol.
  • RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization [ Time Frame: 30 days post randomization ]
    A brief, structured interview regarding health care utilization (inpatient and outpatient) will be used, which collects information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment and self-help sources of support (e.g., NA).
  • RCT Component: Overdose Events at 30 days post randomization [ Time Frame: 30 days post randomization ]
    Assessment of past 30-day overdose events will be completed at 30 days post study enrollment. In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
  • BUP Implementation Component (ED): Change in the number of ED visits during which BUP is administered in the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of ED visits during which BUP is administered in the ED (prior 30 days ) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the umber of ED visits during which BUP is administered in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days ) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of ED visits during which patients receive a prescription for BUP in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are DATA 2000 X-waivered (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who administered BUP in the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of unique ED prescribers who are prescribing BUP from the ED (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the percent adherence to the critical action checklist for ED-initiated SL-BUP and XR-BUP (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP Implementation Component (ED): Change in the number of ED prescribers who fully adhere to the critical action checklist (prior 30 days) [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: Site Initiation to 6 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of programs accepting patients into formal addiction treatment at 7 days following the ED visits [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in number of formal systems (e.g., formal, informal, feedback) pathways in place for arranging referrals for ongoing MOUD. [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in formal addiction treatment at 7 days following the ED visit [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: Baseline to site initiation (up to 8 months post baseline) ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: Site initiation to 6 months post site initiation ]
  • BUP (XR and SL) Implementation Component (Community): Change in proportion of patients engaged in MOUD at 7 days following the ED visit [ Time Frame: 6 months post site initiation to 12 months post site initiation ]
  • Ancillary Component: Desire to Use post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100.
  • Ancillary Component: Bad drug effects post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post injection ]
    The investigators will use a VAS to assess bad drug effects. Participants will be asked to respond to the statement: "At this moment, I feel bad drug effects" and place a mark across the line at the point that corresponds to the extent to which they are feeling any bad drug effects. Anchors will include 0 mm - 'not at all' to 100 mm - 'extremely'.
  • Ancillary Component: Changes in withdrawal severity at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Pre-injection and 240 minutes post-injection ]
    Adjective Rating Scale for Withdrawal (ARSW) - The ARSW is a 16-item self-report scale that measures subjective severity of opioid withdrawal and symptoms using a scale of 1 to 9 (1 is none and 9 is severe).
  • Ancillary Component: Pain at injection site post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Immediately following XR-BUP injection, 30 minutes and 240 minutes post injection ]
    Participants will report the degree of pain at the injection site after the injection is administered using a numerical rating scale ranging from 0 - no pain to 10 - worst possible pain.
  • Ancillary Component: Vital Signs (temperature) post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (temperature) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (blood pressure- systolic) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (systolic blood pressure, mmHg) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (diastolic blood pressure) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (diastolic blood pressure, mmHg) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (pulse rate) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (pulse rate- beats per minute) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (respiratory rate) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (respiratory rate- breaths/min) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Vital Signs (oxygen saturation) post XR-BUP injection at ED Index Visit- (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Vital signs (oxygen saturation- collected while sitting, following a rest period of at least 3 minutes) collected while sitting, following a rest period of at least 3 minutes are used to medically monitor any changes during the 240 minute time frame.
  • Ancillary Component: Changes in withdrawal severity (COWS) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Changes in withdrawal severity (OOWS) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    The Objective Opioid Withdrawal Scale (OOWS) - The OOWS is a validated measure of the severity of opioid withdrawal that consists of 13 objective items.
  • Ancillary Component: Changes in withdrawal severity (ARSW) at post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Adjective Rating Scale for Withdrawal (ARSW) - The ARSW is a 16-item self-report scale that measures subjective severity of opioid withdrawal and symptoms using a scale of 1 to 9 (1 is none and 9 is severe).
  • Ancillary Component: Pupillary diameter post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    This will be assessed via pupillometry. Two measurements should be taken and if they are discrepant by >0.5mm discrepant, the Research Associate will need to repeat assessment until they achieve two consecutive readings with agreement of <0.5mm. The average of the two measurements is entered.
  • Ancillary Component: Provision of post Injection Medications post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    SL-BUP and ancillary medications will be provided according to a uniform protocol. Research Associates (RAs) and nurses will document the timing and provision of all medications received before and during the 4-hour observation period in the ED. In addition, the Research Associate will review the electronic medical record to determine any additional medications or intravenous fluids were administered to the patient during their ED visit and the timing of those medications.
  • Ancillary Component: Precipitated Withdrawal (yes/no) post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: Every 30 minutes for a total of 240 minutes post XR-BUP injection ]
    Precipitated Withdrawal will be documented on the Precipitated Withdrawal Form along with time of occurrence.
  • Ancillary Component: Local Tolerability post XR-BUP injection at ED Index Visit (Day 0) [ Time Frame: At 30 and 240 minutes post XR-BUP injection ]
    The Research Associate will assess the degree of erythema and swelling at the injection site using a 4-point rating scale ranging from 0 - none to 3-severe.
  • Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration [ Time Frame: Within 1 hour post XR-BUP injection ]
  • Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration [ Time Frame: Within 4 hours of XR-BUP administration ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration [ Time Frame: Within 4 hours of XR-BUP administration ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Daily Substance Use (Days 1-6 post injection) [ Time Frame: Days 1-6 post injection ]
    The Daily Substance Use assessment solicits participant use of substances of interest daily via a text-messaging application.
  • Ancillary Component: Desire to Use (Days 1-6 post injection) [ Time Frame: Days 1-6 post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100 (daily via a text-messaging application).
  • Ancillary Component: Presence of opioids, oxycodone, benzodiazepines, cocaine, methamphetamine, amphetamine, ecstasy (MDMA), marijuana (THC), barbiturate, methadone, buprenorphine and fentanyl (7 days post injection) [ Time Frame: 7 days post injection ]
    Urine testing will be performed for the presence of the following drugs: opioids, oxycodone, benzodiazepines, cocaine, methamphetamine, amphetamine, ecstasy (MDMA), marijuana (THC), barbiturate, methadone, buprenorphine, and fentanyl.
  • Ancillary Component: Opioid Withdrawal (7 days post injection) [ Time Frame: 7 days post injection ]
    Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
  • Ancillary Component: Daily Substance Use (7 days post injection) [ Time Frame: 7 days post injection ]
    The Daily Substance Use assessment solicits participant use of substances of interest.
  • Ancillary Component: Desire to Use (7 days post injection) [ Time Frame: 7 days post injection ]
    The investigators will use a visual analogue scale (VAS) "Desire to Use" to assess craving. Participants will be asked "At this moment I desire opioids" and indicate on the line the point that corresponds to the extent to which they desire opioids. Anchors will include 0 mm - "definitely not" to 100 mm - "definitely so". At follow up daily calls they will report a number between 0 and 100
  • Ancillary Component: Injection Site Reactions (7 days post injection) [ Time Frame: 7 days post injection ]
    At 7-day follow up the participant will be queried about pain, itching, discharge and tenderness at the site. Study staff will examine the patient for erythema at the injection.
  • Ancillary Component: Patient satisfaction with BUP (7 days post injection) [ Time Frame: 7 days post injection ]
    Participant satisfaction and preference will be assessed using quantitative and qualitative mixed methods at 7-day follow-up. Satisfaction will be rated on a Likert 1-5 scale by the participant, and preference order ranking to receive ongoing treatment with SL-BUP, preference to receive ongoing treatment with XR-BUP, and preference to not receive any formulation of BUP will be ranked. The investigators will use open-ended questions to explore patient satisfaction, preference and study experience.
  • Ancillary Component: Health Services Utilization (7 days post injection) [ Time Frame: 7 days post injection ]
    A brief, structured interview (not scored) regarding health care utilization (inpatient and outpatient) will be used, which collects information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment and self-help sources of support (e.g., NA).
  • Ancillary Component: Engagement in Treatment (7 days post injection) [ Time Frame: 7 days post injection ]
    At 7 days post enrollment, participants will be asked to report OUD treatment received. Data will be reported on the Engagement in Treatment - Patient Survey (not scored).
  • Ancillary Component: Overdose Events (7 days post injection) [ Time Frame: 7 days post injection ]
    Assessment of past 30-day overdose events will be completed at day 7 In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Emergency Department-Initiated Buprenorphine Validation Network Trial
Official Title  ICMJE Emergency Department-Initiated Buprenorphine Validation Network Trial
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Opioid-use Disorder
Intervention  ICMJE
  • Drug: CAM2038
    Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.
  • Drug: Buprenorphine Sublingual Product

    COWS ≥ 8: Patients will receive 4mg of SL-BUP for a COWS score of 8-12 (mild withdrawal). After 30-45 minutes if tolerated and no unanticipated adverse reactions, an additional 4mg can be administered for a total of 8mg in the ED. Patients presenting with moderate-severe withdrawal (COWS >≥ 13) will receive an initial dose of 8mg SL-BUP. All patients will receive a buprenorphine prescription and instructions for additional BUP doses to allow for up to a dose of 12mg if needed, and for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD (medications for opioid use disorder).

    COWS 4-7: Patients will be provided with a uniform set of instructions to guide unobserved (home) induction. They will be prescribed doses of SL-BUP to allow them to take dose up to 12mg in the 24 hours after discharge. All patients will also receive a buprenorphine prescription for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD.

Study Arms  ICMJE
  • Experimental: XR-BUP
    Injectable buprenorphine
    Intervention: Drug: CAM2038
  • Active Comparator: Standard SL-BUP
    Sublingual buprenorphine
    Intervention: Drug: Buprenorphine Sublingual Product
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 8, 2020)
2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gail D'Onofrio, MD, MS 203-785-7059 gail.donofrio@yale.edu
Contact: David Fiellin, MD 203-737-3347 david.fiellin@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04225598
Other Study ID Numbers  ICMJE 2000026164
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: In line with the National Institutes of Health Helping to End Addiction Long-term (NIH HEAL) Initiative Public Access and Data Sharing Policy, publications and underlying primary data will be made available to the public.
Time Frame: Data will be made available after 1) the primary paper has been accepted for publication, or 2) the data is locked for more than 18 months, whichever comes first.
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE
  • National Drug Abuse Treatment Clinical Trials Network
  • The Emmes Company, LLC
  • Harvard Medical School (HMS and HSDM)
  • University of Pennsylvania
  • NYU Langone Health
  • Icahn School of Medicine at Mount Sinai
  • Alameda Health System
  • Weill Medical College of Cornell University
Investigators  ICMJE
Principal Investigator: Gail D'Onofrio, MD, MS Yale School of Medicine, Department of Emergency Medicine
Principal Investigator: David Fiellin, MD Yale School of Medicine, Department of Internal Medicine
PRS Account Yale University
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP