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

NYU Langone Health

Status and phase: Completed; Phase 4

Conditions: Opioid-use Disorder

Treatments: Drug: XR-B (SUBLOCADETM); Drug: XR-NTX

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04219540

19-01450

Details and patient eligibility

About

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.

Full 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.

Enrollment: 675 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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675 participants in 3 patient groups

extended-release buprenorphine (XR-B)

Experimental group

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.

Treatment:

Drug: XR-B (SUBLOCADETM)

extended release naltrexone XR-NTX

Experimental group

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.

Treatment:

Drug: XR-NTX

Treatment as Usual (TAU)

No Intervention group

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.