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

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: XR-B (SUBLOCADETM); Drug: XR-NTX

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.

• Study Type: Interventional
• Enrollment (Estimated): 796
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ryan McDonald; Phone Number: 646-501-3581; Email: Ryan.mcdonald@nyulangone.org

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University School of Medicine
      • Contact: Sandra Springer, MD; Email: sandra.springer@yale.edu
      • Principal Investigator: Sandra Springer, MD
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Friends Research Institute
      • Contact: Jan Gryczynski, MD; Email: jgryczynski@friendsresearch.org
      • Principal Investigator: Robert Schwartz, MD
  • New Hampshire
    • Hanover, New Hampshire, United States, 03755
      • Recruiting
      • Dartmouth College
      • Contact: Lisa Marsch, PhD; Email: Lisa.A.Marsch@dartmouth.edu
      • Principal Investigator: Lisa Marsch, PhD
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers University
      • Contact: Amesika Nyaku, MD; Email: ann37@njms.rutgers.edu
      • Principal Investigator: Amesika Nyaku, MD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Ryan McDonald; Phone Number: 646-501-3581; Email: Ryan.mcdonald@nyulangone.org
      • Principal Investigator: Joshua Lee, MD, MSc
  • Oregon
    • Portland, Oregon, United States, 97219
      • Recruiting
      • Oregon Health and Science University
      • Contact: Elizabeth Waddell, PhD; Email: waddelle@ohsu.edu
      • Principal Investigator: Elizabeth Waddell, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: extended-release buprenorphine (XR-B); 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.	Drug: XR-B (SUBLOCADETM); 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.; Other Names: SUBLOCADE TM
Experimental: extended release naltrexone XR-NTX; 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.	Drug: XR-NTX; 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; Other Names: Vivitrol®
No Intervention: Treatment as Usual (TAU); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Weeks 1-24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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),	Weeks 0, 4, 8, 12,16, 20, 24, 52
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.	Weeks 0, 4, 8, 12,16, 20, 24, 52
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.	Weeks 0, 4, 8, 12,16, 20, 24, 52
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	Weeks 0, 24
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.	Weeks 4, 8, 12,16, 20, 24, 52
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.	Weeks 4, 8, 12,16, 20, 24, 52
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.	Weeks 4, 8, 12,16, 20, 24, 52

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Joshua Lee, MD, NYU Langone

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2021
• Primary Completion (Estimated): June 15, 2024
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: 19-01450

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No