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High Dose Buprenorphine (BUP) Induction in the Emergency Department (ED)

Primary Purpose

Opioid Use Disorder

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
High Dose Buprenorphine
Standard Buprenorphine Dose
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use Disorder

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
  • Treated in the ED during screening hours
  • Meet DSM-5 diagnostic criteria for moderate to severe OUD
  • Clinical Opioid Withdrawal Score (COWS) score ≥ 8
  • Urine toxicology positive for fentanyl
  • Able to speak English sufficiently to understand study procedures

Exclusion Criteria:

  • UDS positive for methadone.
  • Be pregnant determined by urine human chorionic gonadotropin (uHCG) testing
  • Have an unstable medical or psychiatric condition including suicidality requiring hospitalization
  • Require ongoing opioids for pain management
  • Be enrolled in formal addition treatment including by court order anytime within the last 30 days. Patients enrolled in formal addiction treatment not receiving Medications for Opioid Use Disorder (MOUD) are eligible
  • Be a prisoner or in custody at the time of the index visit
  • Have any pending legal status or pending legal action that could prohibit full participation in or compliance with study procedures.
  • Unable to provide one additional point of contact other than themselves
  • Unwilling to follow study procedures
  • Have prior enrollment in the current study
  • Have a known allergy or hypersensitivity to BUP
  • Have been engaged in formal addiction treatment in the 30-days prior to the ED visit (this does not include addiction treatment or residential programs where MOUD is not given (e.g. behavioral counseling, abstinence programs, NA)
  • Have received naloxone in the 60-minutes prior to the anticipated first transmucosal (TM) BUP administration
  • Is undergoing concurrent treatment with another investigational agent or enrolment in another clinical study

Sites / Locations

  • Barnes Jewish Hospital Emergency Department
  • Mount Sinai Beth IsraelRecruiting
  • Mount Sinai Hospital
  • Rhode Island Hospital Emergency Department

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Buprenorphine Standard Dose

Buprenorphine High Dose

Arm Description

The standard arm will receive an induction dose of 12mg of buprenorphine (BUP) split as 8mg at time=0 and 4mg at time=30-60 min.

The experimental arm tests the safety and tolerability of 32mg of BUP split as 16mg at time=0 and 16mg at time=30-60 min as an induction dose.

Outcomes

Primary Outcome Measures

The proportion of participants engaged in comprehensive addiction treatment at 7-days post-ED induction
The proportion of participants engaged in comprehensive addiction treatment at 7 days post-ED induction as verified by participant and the addiction treatment program.

Secondary Outcome Measures

Percentage of days with opioid abstinence (Trial 1)
Participants' percentage of days with opioid abstinence (defined as negative urine drug screen (UDS)) at day 7 (Trial 1)
Percentage of days with opioid use (Trial 1)
Participants' percentage of days with opioid use at Time-Line Follow Back (TLFB) over 7 days post induction (inclusive) (Trial 1)
Percentage of days with opioid use (Trial 2)
Participants' percentage of days with opioid use at Time-Line Follow Back (TLFB) over 30 days post induction (inclusive) (Trial 2)
Daily assessment of opioid use (Trial 1)
Participants' daily assessment of opioid use out of days over a 7-day period (Trial 1)
Change in number of times opioids used (Trial 1)
Change in participants' number of times opioids were per day used from induction through 7 days follow-up assessment (Trial 1)
Change in number of times opioids used (Trial 2)
Change in participants' number of times opioids were used from baseline to follow-up assessment day 7 (Trial 2)
Change in number of times opioids used (Trial 2)
Change in participants' number of times opioids were used from baseline to follow-up assessment day 30 (Trial 2)
Proportion of participants with persistent nausea/vomiting during induction
Proportion of participants with persistent nausea/vomiting during the induction visit requiring treatment.
Proportion of participants with a Pasero Opioid-induced Sedation Scale (POSS) score of 3 or higher
Proportion of participants with a POSS score of 3 or higher at the conclusion of the induction visit 4-hour observation period. Higher score indicates more severe sedation. S=sleep, easy to arouse awake/alert slight drowsy/easy aroused Frequently drowsy, arousable, drifts off to sleep during conversation Somnolent, minimal or no response to verbal and physical stimulation
Proportion of participants with a Mini Mental Status Exam (MMSE) score indicating severe cognitive impairment
Proportion of participants with a Mini Mental Status Exam (MMSE) indicating severe cognitive impairment at the conclusion of the induction visit 4-hour observation period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language). Full scale ranges from 0-30, with higher scores indicating better function.
Proportion of participants with precipitated or worsening withdrawal
Proportion of participants with precipitated or worsening withdrawal requiring continued treatment with ancillary medications during the induction visit.
Patient Satisfaction Survey
Patient Satisfaction Survey is a 4-item questionnaire, each item scores 1-5, with total score range of 4-20. Higher scores would indicate a higher level of satisfaction.

Full Information

First Posted
October 17, 2022
Last Updated
May 3, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05589181
Brief Title
High Dose Buprenorphine (BUP) Induction in the Emergency Department (ED)
Official Title
Safety and Efficacy of High Dose Buprenorphine Induction in Fentanyl Positive Emergency Department Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 10, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This project, involving two distinct clinical trials, tests whether induction to a higher than currently recommended buprenorphine (BUP) induction dose is safe and can improve the proportion of patients who engage in comprehensive addiction services within 7-day of induction. Trial 1 is a head-to-head comparison of the safety, tolerability and feasibility of high dose BUP induction (32 mg). The study involves two cohorts, (1) a 12mg cohort (standard) to determine baseline data and (2) a 32 mg (high dose) cohort. If the 32mg is intolerable, a 24 mg dose may be evaluated. Trial 2 is a small pilot multicenter randomized, double blinded, clinical trial in 80 participants (randomized 1:1) that will provide preliminary information on efficacy with the primary outcome being engagement in comprehensive addiction treatment 7-days post BUP induction. In collaboration with National Institute on Drug Abuse (NIDA), the research team have determined that there must be a minimum increase in engagement in comprehensive addiction treatment of 15% at 7-days in the high dose induction group to justify a larger future clinical trial.
Detailed Description
The design of Trial 1 and Trial 2 will be described separately. Trial 1 is a prospective test of the safety and tolerability of 32 mg of BUP as an induction dose (split dosing over 30-60 minutes with 4 hours of post-induction monitoring) with the recommended BUP induction dose (12mg, also split over 60 minutes). Dosing for the 12 mg cohort is planned to be 8 mg at t=0 and 4 mg at 30-60 min. The dosing for the 32 mg cohort is planned to be 16 mg at t=0 and 16 mg at 30-60 min. The frequency of unacceptable dose limiting toxicities is set at >10%. The study will therefore compare two cohorts of 10 participants, with the potential for 5 extra participants per cohort if 1 dose limiting toxicity is observed in the first 10 subjects in a cohort. If there are two dose limiting toxicities (DLTs) in the 32mg cohort, that cohort will no longer recruit. A new, 24 mg high dose cohort will be formed. If the 24 mg cohort has 2 DLTs in either 1st 10 patients or when expanded to n=15, it will be concluded that no safe/tolerable high induction dose has been identified and trial 2 will not occur. If the 12 mg (control) cohort has 2 DLTs, at n=15 the Data and Safety Monitoring Board (DSMB) will be consulted about enlarging the cohort size or other modifications. Any participants in the 12 mg cohort who choose not to take their full assigned dose will be replaced to ensure the full cohort size. No more than 20% of participants in either 24 mg or 32 mg cohorts who choose not to take their full assigned dose can be replaced. Trial 1 will only take place in the Emergency Department at Mount Sinai Beth Israel Study participants can only be enrolled if they are active ED patients and only on the day of their ED visits. Patients will be screened by trained research associates (RAs) with a screener that includes questions about illicit opioid use in the past 30 days embedded in a general health and substance use screener that also includes questions about safety, tobacco and alcohol use. The screener will contain questions regarding opioid use and non-medical use of prescription opioids. Potential study patients who report any opioid use in the past month will complete a 7-day recall of such use. If opioid use is reported during the past 7 days a brief (10 minute) structured diagnostic interview with questions on the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria will be used to evaluate the presence of moderate/severe opioid use. Those who meet study criteria will be informed that they may qualify for the study and will be then asked to provide a urine sample. If the urine tests are positive for fentanyl, the patient indicates ability to provide contract information for 1 separate reliable contacts (in addition to their own) and the patient meets all eligibility criteria on the Patient Eligibility Summary form, informed consent will be obtained. Patients who sign written informed consent will be enrolled in the study and assigned to a dose cohort (either 12 or 32mg). Assignment in Trial 1 is sequential, not randomized. Participants will receive their full dose over 30-60 minutes and be observed for a total of 4-hours in the ED from the time of their first BUP dose. At the time of discharge all participants will receive a prescription for BUP for 7-day (16mg per day), harm reduction counseling that includes the provision of a naloxone rescue kit and fentanyl test strips and a referral for out-patient addiction treatment within 7-days of the ED visit. After discharge, study participants will be followed-up daily for 7 days to assess daily drug use and opioid craving. At 7-days all participants will be asked to return to provide a urine drug screen and be assessed for engagement in comprehensive addiction treatment and healthcare utilization. Trial 2 is a four-site pilot randomized controlled trial (RCT) (n=20x4) conducted in the ED, that will test the efficacy, safety and tolerability of the high BUP dose (selected in Trial 1) as an induction dose (split dosing over 30-60 min) compared standard BUP induction dose (up to 12mg) also split over 30-60 min. The four sites participating in the Trial 2 RCT are, (1) Mount Sinai Hospital Emergency Department, (2) Mount Sinai Beth Israel Emergency Department, (3) Barnes Jewish Hospital Emergency Department and (4) Rhode Island Hospital Emergency Department. Eligibility, screening and enrollment procedures are identical to Trial 1. Eligible participants will be randomized 1:1 with stratification by site to receive either standard (12mg) or high dose BUP induction (determined from trial 1 but no more than 32mg). Participants and study personnel will be blinded to group assignment. All participants will be observed in the ED for a total of 4-hours from the time of their first BUP dose. At discharge. all participants will receive a prescription for BUP for 7-day (16mg per day), harm reduction counseling that includes the provision of a naloxone rescue kit and fentanyl test strips and a referral for out-patient addiction treatment within 7-days of the ED visit. Participants will be followed-up at 7 and 14-day to assess the primary outcome (engagement in comprehensive addiction treatment) and multiple secondary outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The design of Trial 1 and Trial 2 will be described separately. Trial 1 is a prospective test of the safety and tolerability of 32 mg of BUP as an induction dose (split dosing over 30-60 minutes with 4 hours of post-induction monitoring) with the recommended BUP induction dose (12mg, also split over 60 minutes). Trial 2 is a four-site pilot RCT (n=20x4) conducted in the ED, that will test the efficacy, safety and tolerability of the high BUP dose (selected in Trial 1) as an induction dose (split dosing over 30-60 min) compared to standard BUP induction dose (up to 12mg) also split over 30-60 min. The four sites participating in the Trial 2 RCT are, (1) Mount Sinai Hospital Emergency Department, (2) Mount Sinai Beth Israel Emergency Department, (3) Barnes Jewish Hospital Emergency Department and (4) Rhode Island Hospital Emergency Department.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
In trial 1 neither the investigator nor the participant will be blinded to group assignment. In Trial 2, participants, Investigators and site personnel with the exception of the investigational drug pharmacist will be blinded to group assignment.
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Buprenorphine Standard Dose
Arm Type
Active Comparator
Arm Description
The standard arm will receive an induction dose of 12mg of buprenorphine (BUP) split as 8mg at time=0 and 4mg at time=30-60 min.
Arm Title
Buprenorphine High Dose
Arm Type
Experimental
Arm Description
The experimental arm tests the safety and tolerability of 32mg of BUP split as 16mg at time=0 and 16mg at time=30-60 min as an induction dose.
Intervention Type
Drug
Intervention Name(s)
High Dose Buprenorphine
Intervention Description
32mg of BUP split as 16mg at 0 minutes and 16mg at 30-60 min as an induction dose
Intervention Type
Drug
Intervention Name(s)
Standard Buprenorphine Dose
Intervention Description
12mg of buprenorphine (BUP) split as 8mg at 0 minutes and 4mg at time 30-60 min as an induction dose
Primary Outcome Measure Information:
Title
The proportion of participants engaged in comprehensive addiction treatment at 7-days post-ED induction
Description
The proportion of participants engaged in comprehensive addiction treatment at 7 days post-ED induction as verified by participant and the addiction treatment program.
Time Frame
7 days post-ED visit
Secondary Outcome Measure Information:
Title
Percentage of days with opioid abstinence (Trial 1)
Description
Participants' percentage of days with opioid abstinence (defined as negative urine drug screen (UDS)) at day 7 (Trial 1)
Time Frame
at day 7
Title
Percentage of days with opioid use (Trial 1)
Description
Participants' percentage of days with opioid use at Time-Line Follow Back (TLFB) over 7 days post induction (inclusive) (Trial 1)
Time Frame
7 days post-ED
Title
Percentage of days with opioid use (Trial 2)
Description
Participants' percentage of days with opioid use at Time-Line Follow Back (TLFB) over 30 days post induction (inclusive) (Trial 2)
Time Frame
30 days post-ED
Title
Daily assessment of opioid use (Trial 1)
Description
Participants' daily assessment of opioid use out of days over a 7-day period (Trial 1)
Time Frame
Days 1-7 after enrollment
Title
Change in number of times opioids used (Trial 1)
Description
Change in participants' number of times opioids were per day used from induction through 7 days follow-up assessment (Trial 1)
Time Frame
induction through 7 days
Title
Change in number of times opioids used (Trial 2)
Description
Change in participants' number of times opioids were used from baseline to follow-up assessment day 7 (Trial 2)
Time Frame
Baseline and follow-up assessment day 7
Title
Change in number of times opioids used (Trial 2)
Description
Change in participants' number of times opioids were used from baseline to follow-up assessment day 30 (Trial 2)
Time Frame
Baseline and follow-up assessment day 30
Title
Proportion of participants with persistent nausea/vomiting during induction
Description
Proportion of participants with persistent nausea/vomiting during the induction visit requiring treatment.
Time Frame
at 240 minutes
Title
Proportion of participants with a Pasero Opioid-induced Sedation Scale (POSS) score of 3 or higher
Description
Proportion of participants with a POSS score of 3 or higher at the conclusion of the induction visit 4-hour observation period. Higher score indicates more severe sedation. S=sleep, easy to arouse awake/alert slight drowsy/easy aroused Frequently drowsy, arousable, drifts off to sleep during conversation Somnolent, minimal or no response to verbal and physical stimulation
Time Frame
at 240 minutes
Title
Proportion of participants with a Mini Mental Status Exam (MMSE) score indicating severe cognitive impairment
Description
Proportion of participants with a Mini Mental Status Exam (MMSE) indicating severe cognitive impairment at the conclusion of the induction visit 4-hour observation period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language). Full scale ranges from 0-30, with higher scores indicating better function.
Time Frame
at 240 minutes
Title
Proportion of participants with precipitated or worsening withdrawal
Description
Proportion of participants with precipitated or worsening withdrawal requiring continued treatment with ancillary medications during the induction visit.
Time Frame
up to 240 minutes
Title
Patient Satisfaction Survey
Description
Patient Satisfaction Survey is a 4-item questionnaire, each item scores 1-5, with total score range of 4-20. Higher scores would indicate a higher level of satisfaction.
Time Frame
ED enrollment visit at 240 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study Treated in the ED during screening hours Meet DSM-5 diagnostic criteria for moderate to severe OUD Clinical Opioid Withdrawal Score (COWS) score ≥ 8 Urine toxicology positive for fentanyl Able to speak English sufficiently to understand study procedures Exclusion Criteria: UDS positive for methadone. Be pregnant determined by urine human chorionic gonadotropin (uHCG) testing Have an unstable medical or psychiatric condition including suicidality requiring hospitalization Require ongoing opioids for pain management Be enrolled in formal addition treatment including by court order anytime within the last 30 days. Patients enrolled in formal addiction treatment not receiving Medications for Opioid Use Disorder (MOUD) are eligible Be a prisoner or in custody at the time of the index visit Have any pending legal status or pending legal action that could prohibit full participation in or compliance with study procedures. Unable to provide one additional point of contact other than themselves Unwilling to follow study procedures Have prior enrollment in the current study Have a known allergy or hypersensitivity to BUP Have been engaged in formal addiction treatment in the 30-days prior to the ED visit (this does not include addiction treatment or residential programs where MOUD is not given (e.g. behavioral counseling, abstinence programs, NA) Have received naloxone in the 60-minutes prior to the anticipated first transmucosal (TM) BUP administration Is undergoing concurrent treatment with another investigational agent or enrolment in another clinical study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ethan Cowan, MD, MS
Phone
212-420-2652
Email
ethan.cowan@mountsinai.org
First Name & Middle Initial & Last Name or Official Title & Degree
Clare O'Brien-Lambert
Phone
347-415-5407
Email
clare.obrien-lambert@mountsinai.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ethan Cowan, MD, MS
Organizational Affiliation
Icahn School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barnes Jewish Hospital Emergency Department
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Mount Sinai Beth Israel
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ethan Cowan, MD, MS
Phone
212-420-2652
Email
ethan.cowan@mountsinai.org
First Name & Middle Initial & Last Name & Degree
Clare O'Brien-Lambert
Phone
347-415-5407
Email
clare.obrien-lambert@moutnsinai.org
First Name & Middle Initial & Last Name & Degree
Ethan Cowan
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Rhode Island Hospital Emergency Department
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. This study will share deidentified individual participant data that underlie the results that are reported. The data intended for broader use will be free of identifiers that would permit linkages to individual research participants and variables that could lead to deductive disclosure of the identity of individual subjects.
IPD Sharing Time Frame
Beginning upon acceptance for publication and ending 5 years following article publication.
IPD Sharing Access Criteria
deidentified individual patient data (IPD) will be shared with researchers who provide a methodologically sound proposal for the purpose of achieving aims in the approved proposal. Proposals should be directed to ethan.cowan@mountsinai.org.

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High Dose Buprenorphine (BUP) Induction in the Emergency Department (ED)

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