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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 : Not yet recruiting
First Posted : January 13, 2020
Last Update Posted : June 16, 2020
Sponsor:
Collaborators:
National Drug Abuse Treatment Clinical Trials Network
The Emmes Company, LLC
Harvard Medical School
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

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.

Condition or disease Intervention/treatment Phase
Opioid-use Disorder Drug: CAM2038 Drug: Buprenorphine Sublingual Product Phase 2

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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Emergency Department-Initiated Buprenorphine Validation Network Trial
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: XR-BUP
Injectable buprenorphine
Drug: CAM2038
Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.

Active Comparator: Standard SL-BUP
Sublingual buprenorphine
Drug: Buprenorphine Sublingual Product
Patients will receive 4mg of SL-BUP for a COWS score of 8-12 (mild withdrawal). After 45-60 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 a maximum dose of 12mg on Day 0 if needed, and for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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)

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. 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) ]
  14. 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 ]
  15. 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 ]
  16. 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) ]
  17. 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 ]
  18. 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 ]
  19. 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) ]
  20. 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 ]
  21. 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 ]
  22. 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) ]
  23. 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 ]
  24. 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 ]
  25. 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) ]
  26. 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 ]
  27. 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 ]
  28. 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) ]
  29. 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 ]
  30. 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 ]
  31. 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) ]
  32. 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 ]
  33. 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 ]
  34. 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) ]
  35. 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 ]
  36. 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 ]
  37. 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) ]
  38. 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 ]
  39. 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 ]
  40. 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) ]
  41. 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 ]
  42. 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 ]
  43. 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) ]
  44. 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 ]
  45. 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 ]
  46. 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.

  47. 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'.

  48. 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).

  49. 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.

  50. 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.

  51. 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.

  52. 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.

  53. 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.

  54. 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.

  55. 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.

  56. 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.

  57. 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.

  58. 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).

  59. 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.

  60. 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.

  61. 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.

  62. 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.

  63. 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 ]
  64. 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.

  65. 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.

  66. 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.

  67. 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).

  68. 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.

  69. 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.

  70. 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.

  71. 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

  72. 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.

  73. 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.

  74. 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).

  75. 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).

  76. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 > 8
  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 at the index ED visit, prior to randomization
  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 14 days) enrolled in formal addiction treatment, including by court order. Patients enrolled in formal addiction who 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 contact referral provider/program or unavailable for the follow-up assessments)
  11. 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 will not be eligible unless urine toxicology testing is performed with a method approved for clinical use
  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 an index ED visit due to opioid overdose
  2. Have a urine toxicology test that is positive for methadone
  3. Be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit
  4. Have a medical or psychiatric condition that requires hospitalization at the index ED visit, prior to enrollment
  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 treatment but 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 answer daily assessments until day 7)
  12. Have prior enrollment in the current study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04225598


Contacts
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Contact: Gail D'Onofrio, MD, MS 203-785-4404 gail.donofrio@yale.edu
Contact: David Fiellin, MD 203-737-3347 david.fiellin@yale.edu

Locations
Show Show 35 study locations
Sponsors and Collaborators
Yale University
National Drug Abuse Treatment Clinical Trials Network
The Emmes Company, LLC
Harvard Medical School
University of Pennsylvania
NYU Langone Health
Icahn School of Medicine at Mount Sinai
Alameda Health System
Weill Medical College of Cornell University
Investigators
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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
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT04225598    
Other Study ID Numbers: 2000026164
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yale University:
Opioid-use Disorder
Additional relevant MeSH terms:
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Emergencies
Disease Attributes
Pathologic Processes
Buprenorphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists