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Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults

Primary Purpose

Opioid-use Disorder

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
XR-B (SUBLOCADETM)
XR-NTX
Sponsored by
NYU Langone Health
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:

XR-B vs. XR-NTX Inclusions:

  1. Adult volunteer aged 18-65yo able to provide written informed consent in English (or Spanish at some sites)
  2. Current CJS incarceration (residing in a controlled environment) with pending release date (within 6 months of randomization)
  3. Current or history of moderate-to-severe opioid use disorder in the past year prior to incarceration (OUD, DSM-5)
  4. Not planning to move out of state or to new location within 6-months post-release.
  5. Willing to accept either XR-B or XR-NTX assignment.

Non-randomized TAU Inclusions:

  1. Recruited prior to launch of RCT or not willing to randomize to XR-B or XR-NTX assignment, but are otherwise eligible based on inclusion (#2-4) and exclusion below (#6-10)
  2. Adult volunteer aged 18-65yo able to provide written informed consent in English or Spanish
  3. Current CJS incarceration with pending release date
  4. Current or history of moderate-to-severe opioid use disorder in the past year prior to incarceration (OUD, DSM-5)
  5. Not planning to move out of state or to new location within 6-months post-release.

    Exclusion Criteria:

    XR-B vs. XR-NTX Exclusions:

  6. Medical or psychiatric disorders making participation unsafe or regular follow-up unlikely, (such as suicidal ideation or pre-existing moderate to severe hepatic impairment)
  7. Pregnancy, planning conception, or breast-feeding
  8. Allergy, hypersensitivity or medical contraindication to either medication
  9. Chronic pain requiring opioid pain management
  10. On daily stable methadone or buprenorphine (SL-B) maintenance every day for past 30 days prior to incarceration or monthly XR-NTX or XR-BUP one month prior to incarceration AND intending to remain on methadone or buprenorphine or XR-NTX maintenance upon return to the community.

Non-randomized TAU Exclusions:

6. Severe medical or psychiatric disorders, such as suicidal ideation or moderate to severe hepatic impairment 7. Pregnancy, planning conception, or breast-feeding 8. Allergy, hypersensitivity or medical contraindication to either medication 9. Chronic pain requiring opioid pain management 10. On daily stable methadone or buprenorphine (SL-B) maintenance every day for past 30 days prior to incarceration or monthly XR-NTX or XR-BUP one month prior to incarceration AND intending to remain on methadone or buprenorphine or XR-NTX maintenance upon return to the community.

Sites / Locations

  • Yale University School of MedicineRecruiting
  • Friends Research InstituteRecruiting
  • Dartmouth CollegeRecruiting
  • Rutgers UniversityRecruiting
  • NYU Langone HealthRecruiting
  • Oregon Health and Science UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

extended-release buprenorphine (XR-B)

extended release naltrexone XR-NTX

Treatment as Usual (TAU)

Arm Description

Subjects who agree to XR-B treatment will receive an XR-B injection to the abdomen. The injection is a liquid medication in the amount of either 100 or 300 mg buprenorphine in 1.5 cc volume and will last in the body for about 30 days. The medication is stored in a small nodule under the skin of the belly where it was injected. The buprenorphine is gradually released into the body over time for a 30-day period.

Subjects who agree to XR-NTX treatment will receive an injection of XR-NTX to the outer upper part of your buttock. The injection is a liquid medication in the amount of 380 mg naltrexone in 4 cc volume (about 1 teaspoon) and will last in your body for about 30 days. Following release, visits with study physicians at Bellevue Hospital will offer further counseling or medication treatment referrals, the option to receive additional XR-NTX injections once a month following the first injection and continued encouragement to avoid relapses and stay on treatment.

In this group you will not receive any study medication. You will be able to receive any treatments available to individuals in the jail or prison who are not in the study. Trained study staff at the first two visits will provide counseling focusing on relapse and overdose prevention, treatment engagement, and navigating re-entry challenges.

Outcomes

Primary Outcome Measures

Change in effectiveness of XR-B versus XR-NTX
The primary outcome measure is the number of injections during the 24-week post-release treatment phase, range 0-6. The comparison of the two arms will be based on the log-odds ratio of the injection rate for participants randomized to XR-B vs. XR-N. Retention is defined as the proportion of scheduled study medication injections received (range, 0-6). For the primary outcome, less than 6 XR-B injections will contribute to lower retention (<5 of 6), and 7+ XR-NTX will contribute only to maximum retention (6 of 6).

Secondary Outcome Measures

Change in Opioid use
Change in opioid treatment outcomes will assess for illicit opioid use through self-reported opioid use (days per month), opioid-positive urine samples (negative vs. positive or missing, monthly), and overdose events (fatal and non-fatal),
Change in Opioid treatment outcomes - adverse events
Change in Opioid use will be tracked monthly through non-fatal and fatal overdose events and other adverse events and death recorded on the Opioid Overdose AE form and the Opioid relapse outcome form.
Change in Opioid treatment outcomes - lifestyle changes
Non-study addiction treatment participation, depression scores (Hamilton Depression scale) and quality of life (WHOQOL) changes will be assessed for demographic, housing, employment status changes.
Change in Opioid treatment outcomes - HIV changes
Changes in HIV sex and IVDU risk scores as well as HIV and HCV status will be assessed HIV/HCV risk behaviors (RAB), HIV P24ag/ ab with reflex HIV RNA (if HIV ab negative at baseline; if HIV AB positive at baseline just check HIV RNA) and HCVAb with reflex HCV RNA if AB positive ( if AB + at baseline then just HCV VL at f/u timepoints) at baseline week 24 and week 52
Change in criminal justice system (CJS) involvement with XR-B versus XR-NTX
Criminal justice system (CJS) involvement and recidivism outcomes will be measured by the number of new criminal charges, new arrests, re-incarceration episodes, and re-incarceration days by CJS public records audits. XR-B may be an effective CJS intervention alongside other OUD medications and may ultimately allow for much wider uptake of opioid agonist medication treatments in CJS populations in comparison to XR-NTX.
Change in Non-randomized Treatment-As-Usual retention compared to XR-B/XR-N.
TAU participants in this trial will be followed similarly to randomized participants but will not receive study medication or active medical treatment from the study. Prior to release from correctional controlled environment and at research visit follow-up in the community, all TAU participants will be provided education and materials that include information on opioid overdose prevention and referrals to other community addiction treatment services. TAU participants will receive the same visit incentives and study team contact, including Tracker services, as randomized participants. This amount of contact, incentives, education, and referrals are likely in excess than actual real-world 'usual care' of opioid use disorder patients released from a CJS controlled environment, and is in keeping with ethical standards for clinical trials among prisoners, in which all experimental arms must receive some tangible yet non-coercive benefit beyond usual care.
Change in Non-randomized Treatment-As-Usual rates of OUD
TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications. TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications.

Full Information

First Posted
November 26, 2019
Last Updated
March 6, 2023
Sponsor
NYU Langone Health
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT04219540
Brief Title
Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults
Official Title
Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 7, 2021 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study seeks to compare the effectiveness of two medications used to treat opioid use disorder, extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX), among adults currently incarcerated in U.S. jails and prisons at 5 distinct trial sites. This open-label, non-inferiority, head-to-head study design will offer providers, correctional and public health authorities, payers and policy makers' timely and relevant data to assess the effectiveness of XR-B (and XR-NTX) as potentially useful re-entry and relapse prevention treatment options. It is hypothesized that XR-B is non-inferior to XR-NTX when comparing retention-in-study-medication treatment options.
Detailed Description
Participants eligible for randomization will be randomized 1:1 to extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) prior to release from the correctional controlled environment (including jails, prisons, work release and residential treatment, or other correctional facilities) and treated for 24-weeks following release or upon entry into a community CJS-mandated program. XR-B (SublocadeTM, Indivior) is a partial opioid agonist indicated for the treatment of moderate to severe opioid use disorder. Delivered as a pre-filled 2cc subcutaneous monthly injection, typically using two 300mg/1.5 ml initial starting doses followed by 100mg/0.5 ml monthly maintenance doses. The study will provide up to six monthly XR-B doses throughout the study. Prior to an initial injection, the participant must be stable for seven days or longer on sublingual buprenorphine (SLB) at doses of 8mg/day or higher. Description of Study Intervention Participants eligible for randomization (n=670) will be randomized 1:1 to extended-release buprenorphine (XR-B) vs. extended-release naltrexone (XR-NTX) prior to release from the correctional controlled environment (including jails, prisons, work release and residential treatment, or other correctional facilities) and treated for 24-weeks following release or upon entry into a community CJS-mandated program. XR-B (SublocadeTM, Indivior) is a partial opioid agonist indicated for the treatment of moderate to severe opioid use disorder. Delivered as a pre-filled 2cc subcutaneous monthly injection, typically using two 300mg/1.5 ml initial starting doses followed by 100mg/0.5 ml monthly maintenance doses. The study will provide up to six monthly XR-B doses throughout the study. Prior to an initial injection, the participant must be stable for seven days or longer on sublingual buprenorphine (SLB) at doses of 8mg/day or higher. XR-NTX (Vivitrol®, Alkermes) is an opioid antagonist indicated for the prevention of opioid dependence, following detoxification. A negative opioid urine toxicology, negative self-report of any recent opioid use, and a naloxone challenge. The naloxone challenge consists of 0.4-0.8mg of IV/SC/IM naloxone followed by the observation of no opioid withdrawal symptoms, or the use of oral naltrexone (12.5-25mg) followed by 1-2 hours of observation. XR-NTX is delivered as a 380mg (4cc) intramuscular injection to the upper outer gluteus (buttock) monthly. The study will provide six or more monthly XR-NTX doses.

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 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
301 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
extended-release buprenorphine (XR-B)
Arm Type
Experimental
Arm Description
Subjects who agree to XR-B treatment will receive an XR-B injection to the abdomen. The injection is a liquid medication in the amount of either 100 or 300 mg buprenorphine in 1.5 cc volume and will last in the body for about 30 days. The medication is stored in a small nodule under the skin of the belly where it was injected. The buprenorphine is gradually released into the body over time for a 30-day period.
Arm Title
extended release naltrexone XR-NTX
Arm Type
Experimental
Arm Description
Subjects who agree to XR-NTX treatment will receive an injection of XR-NTX to the outer upper part of your buttock. The injection is a liquid medication in the amount of 380 mg naltrexone in 4 cc volume (about 1 teaspoon) and will last in your body for about 30 days. Following release, visits with study physicians at Bellevue Hospital will offer further counseling or medication treatment referrals, the option to receive additional XR-NTX injections once a month following the first injection and continued encouragement to avoid relapses and stay on treatment.
Arm Title
Treatment as Usual (TAU)
Arm Type
No Intervention
Arm Description
In this group you will not receive any study medication. You will be able to receive any treatments available to individuals in the jail or prison who are not in the study. Trained study staff at the first two visits will provide counseling focusing on relapse and overdose prevention, treatment engagement, and navigating re-entry challenges.
Intervention Type
Drug
Intervention Name(s)
XR-B (SUBLOCADETM)
Other Intervention Name(s)
SUBLOCADE TM
Intervention Description
XR-B (SUBLOCADETM) contains buprenorphine, a partial opioid agonist, and is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a transmucosal buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. Following induction and dose adjustment with sublingual buprenorphine, the recommended starting dose is 300 mg monthly for the first two months followed by a maintenance dose of 100 mg monthly thereafter. XR-B is administered monthly only by subcutaneous injection in the abdominal region. Study clinical staff will have flexibility to continue the 300mg dose for greater than 2 months, or use the 100mg dose for initial induction, if the participant's opioid use history or clinical status at the time of dosing support these decisions.
Intervention Type
Drug
Intervention Name(s)
XR-NTX
Other Intervention Name(s)
Vivitrol®
Intervention Description
XR-NTX (Vivitrol®) produces a 30-day mu opioid receptor antagonist blockade Induction procedures require detoxification off opioids (5-7 days since last opioid use), a negative opioid urine toxicology, negative self-report of any recent opioid use, and a naloxone challenge. The naloxone challenge consists of 0.4-0.8mg of IV/SC/IM naloxone followed by the observation of no opioid withdrawal symptoms, or the use of oral naltrexone (12.5-25mg) followed by 1-2 hours of observation. XR-NTX is then delivered as a 380mg (4cc) intramuscular injection to the upper outer gluteus (buttock). Study interventions are FDA-approved, used in accordance with FDA-labeling and will be administered by a study clinician
Primary Outcome Measure Information:
Title
Change in effectiveness of XR-B versus XR-NTX
Description
The primary outcome measure is the number of injections during the 24-week post-release treatment phase, range 0-6. The comparison of the two arms will be based on the log-odds ratio of the injection rate for participants randomized to XR-B vs. XR-N. Retention is defined as the proportion of scheduled study medication injections received (range, 0-6). For the primary outcome, less than 6 XR-B injections will contribute to lower retention (<5 of 6), and 7+ XR-NTX will contribute only to maximum retention (6 of 6).
Time Frame
Weeks 1-24
Secondary Outcome Measure Information:
Title
Change in Opioid use
Description
Change in opioid treatment outcomes will assess for illicit opioid use through self-reported opioid use (days per month), opioid-positive urine samples (negative vs. positive or missing, monthly), and overdose events (fatal and non-fatal),
Time Frame
Weeks 0, 4, 8, 12,16, 20, 24, 52
Title
Change in Opioid treatment outcomes - adverse events
Description
Change in Opioid use will be tracked monthly through non-fatal and fatal overdose events and other adverse events and death recorded on the Opioid Overdose AE form and the Opioid relapse outcome form.
Time Frame
Weeks 0, 4, 8, 12,16, 20, 24, 52
Title
Change in Opioid treatment outcomes - lifestyle changes
Description
Non-study addiction treatment participation, depression scores (Hamilton Depression scale) and quality of life (WHOQOL) changes will be assessed for demographic, housing, employment status changes.
Time Frame
Weeks 0, 4, 8, 12,16, 20, 24, 52
Title
Change in Opioid treatment outcomes - HIV changes
Description
Changes in HIV sex and IVDU risk scores as well as HIV and HCV status will be assessed HIV/HCV risk behaviors (RAB), HIV P24ag/ ab with reflex HIV RNA (if HIV ab negative at baseline; if HIV AB positive at baseline just check HIV RNA) and HCVAb with reflex HCV RNA if AB positive ( if AB + at baseline then just HCV VL at f/u timepoints) at baseline week 24 and week 52
Time Frame
Weeks 0, 24
Title
Change in criminal justice system (CJS) involvement with XR-B versus XR-NTX
Description
Criminal justice system (CJS) involvement and recidivism outcomes will be measured by the number of new criminal charges, new arrests, re-incarceration episodes, and re-incarceration days by CJS public records audits. XR-B may be an effective CJS intervention alongside other OUD medications and may ultimately allow for much wider uptake of opioid agonist medication treatments in CJS populations in comparison to XR-NTX.
Time Frame
Weeks 4, 8, 12,16, 20, 24, 52
Title
Change in Non-randomized Treatment-As-Usual retention compared to XR-B/XR-N.
Description
TAU participants in this trial will be followed similarly to randomized participants but will not receive study medication or active medical treatment from the study. Prior to release from correctional controlled environment and at research visit follow-up in the community, all TAU participants will be provided education and materials that include information on opioid overdose prevention and referrals to other community addiction treatment services. TAU participants will receive the same visit incentives and study team contact, including Tracker services, as randomized participants. This amount of contact, incentives, education, and referrals are likely in excess than actual real-world 'usual care' of opioid use disorder patients released from a CJS controlled environment, and is in keeping with ethical standards for clinical trials among prisoners, in which all experimental arms must receive some tangible yet non-coercive benefit beyond usual care.
Time Frame
Weeks 4, 8, 12,16, 20, 24, 52
Title
Change in Non-randomized Treatment-As-Usual rates of OUD
Description
TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications. TAU participants, particularly those not in treatment with an OUD medication, may well face higher risk of relapse and overdose vs. active randomized participants receiving study medications.
Time Frame
Weeks 4, 8, 12,16, 20, 24, 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: XR-B vs. XR-NTX Inclusions: (1) Adult volunteer aged 18 years or older able to provide written informed consent in English (or Spanish at some sites) (2) Current CJS incarceration (residing in a controlled environment) with pending release date (within 6 months of randomization) OR community CJS-involvement defined as: a) Current CJS incarceration (residing in a controlled environment) with pending release date (within 6 months of anticipated randomization), or; b) Community-dwelling volunteers with current CJS-involvement. [Current CJS-involvement is defined as either 1) release from any CJS incarceration or detention, or 2) under community supervision (includes parole, probation, drug or other treatment court, or other alternative to incarceration supervision) within 6 months prior to study enrollment (the date of a signed ICF)]. (3) Current or history of moderate-to-severe opioid use disorder in the past year prior to incarceration (OUD, DSM-5) (4) Not planning to move out of state or to new location within 6-months post-release (reasonable chance they can complete 6 months of follow-up visits). (5) Willing to accept either XR-B or XR-NTX assignment. Non-randomized TAU Inclusions: • Recruited prior to launch of RCT or not interested in or appropriate for randomization to XR-B or XR-NTX assignment (i.e, already on methadone pre-release), but are otherwise eligible based on inclusion (#1-4, above) and exclusion (#6-10, below). Exclusion Criteria: XR-B vs. XR-NTX Exclusions: (6) Medical or psychiatric disorders making participation unsafe or regular follow-up unlikely, (such as suicidal ideation or pre-existing moderate to severe hepatic impairment) (7) Pregnancy, planning conception, or breast-feeding (8) Allergy, hypersensitivity or medical contraindication to either medication (9) Chronic pain requiring opioid pain management (10) On daily stable methadone or buprenorphine (SL-B) maintenance every day for past 30 days prior to incarceration or monthly XR-NTX or XR-BUP 30 days or longer prior to incarceration AND intending to remain on same form of methadone or buprenorphine or XR-NTX maintenance now and upon return to the community (i.e., was in MOUD treatment pre-incarceration, on same MOUD treatment now, and plans to continue same MOUD treatment post-incarceration). (Note - If community-dwelling, already on non-study methadone, buprenorphine, or naltrexone for 30 days or longer at the time of enrollment, and planning on continuing same.) Non-randomized TAU Exclusions: • Currently treated with non-study MOUD while currently incarcerated and for 30+ days prior to incarceration, or, if community-dwelling, currently on MOUD for 30 days or longer at the time of enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ryan McDonald
Phone
646-501-3581
Email
Ryan.mcdonald@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua Lee, MD
Organizational Affiliation
NYU Langone
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Springer, MD
Email
sandra.springer@yale.edu
First Name & Middle Initial & Last Name & Degree
Sandra Springer, MD
Facility Name
Friends Research Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Gryczynski, MD
Email
jgryczynski@friendsresearch.org
First Name & Middle Initial & Last Name & Degree
Robert Schwartz, MD
Facility Name
Dartmouth College
City
Hanover
State/Province
New Hampshire
ZIP/Postal Code
03755
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Marsch, PhD
Email
Lisa.A.Marsch@dartmouth.edu
First Name & Middle Initial & Last Name & Degree
Lisa Marsch, PhD
Facility Name
Rutgers University
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amesika Nyaku, MD
Email
ann37@njms.rutgers.edu
First Name & Middle Initial & Last Name & Degree
Amesika Nyaku, MD
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ryan McDonald
Phone
646-501-3581
Email
Ryan.mcdonald@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Joshua Lee, MD, MSc
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Waddell, PhD
Email
waddelle@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Elizabeth Waddell, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Immediately following publication. No end date.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal. Upon reasonable request. Requests should be directed to mia.malone@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Learn more about this trial

Long-acting Buprenorphine vs. Naltrexone Opioid Treatments in CJS-involved Adults

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