CTN - 0051: Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT)

The overarching goal of CTN-0051 is to foster adoption of new relapse-prevention pharmacotherapies in community-based treatment programs (CTPs) where these could have a substantial public health impact. To this end CTN-0051 will assess the comparative effectiveness of extended-release injectable naltrexone (XR-NTX, Vivitrol®), an opioid antagonist recently approved and indicated for the prevention of relapse to opioid dependence, versus buprenorphine-naloxone (BUP-NX, Suboxone®), a high affinity partial agonist indicated for maintenance treatment of opioid dependence, as pharmacotherapeutic aids to recovery.

The study is conducted in 8 CTN-affiliated CTPs that provide or partner with detoxification services (inpatient/residential) which have the capacity to maintain participants opioid-free for approximately 3-7 days, have the capacity to provide medication-assisted therapy, and can provide a minimum of one group or individual counseling session per week during the 24-week treatment period. Up to 600 eligible participants will be randomized to treatment with XR-NTX or BUP-NX for 24 weeks (sufficient to include 350 participants who are randomized more than 72 hours after their last opioid). To maximize generalizability, the point of randomization is flexible, from shortly after program admission until just prior to program discharge.

The primary goal of the study is to estimate the difference, if one exists, between XR-NTX and BUP-NX in the distribution of the time to relapse (i.e., loss of persistent abstinence) during the 6-month trial. The primary outcome measure is the time to the event, with the event called relapse. Secondary objectives are to: (1) compare outcome on XR-NTX versus BUP-NX across a range of clinical safety and secondary efficacy domains, (2) explore demographic, clinical, and genetic predictors of successful treatment and moderators of differential effectiveness (i.e., what variables may help clinicians choose which of these treatments is best for a given patient), and (3) collect a limited dataset to permit analyses of economic costs and benefits of the two treatments.

• Study Design:
  • Clinical Trial
• Study Type:
  • Multicenter
  • Randomized Controlled Clinical Trial
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 638
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Gene
• PMC
• Clinical Trials
  • NCT02032433

Inclusion criteria:

1. Male or female
2. 18 years of age and older
3. Meet DSM-5 criteria for opioid-use disorder (heroin and/or prescription opioids)
4. Have used opioids other than as specifically prescribed within thirty days prior to consent
5. Seeking treatment for opioid dependence and willing to accept "agonist-based" or "antagonist-based" therapy
6. In good-enough general health, as determined by the study physician on the basis of medical history, review of systems, physical exam and laboratory assessments, to permit treatment with XR-NTX or BUP-NX
7. Able to provide written informed consent
8. Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study
9. If female of childbearing potential, be willing to practice an effective method of birth control for the duration of participation in the study

Exclusion criteria:

1. Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study. Examples include:
1. Disabling or terminal medical illness (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease) as assessed by medical history, review of systems, physical exam and/or laboratory assessments
2. Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview
3. Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use likely to require a complicated medical detoxification (routine alcohol and sedative detoxifications may be included)
2. LFTs (ALT, AST) greater than 5 times upper limit of normal
3. Suicidal or homicidal ideation that requires immediate attention
4. Known allergy or sensitivity to buprenorphine, naloxone, naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol® diluent
5. Maintenance on methadone at doses of 30mg or greater at the time of signing consent
6. Presence of pain of sufficient severity as to require ongoing pain management with opioids
7. Pending legal action or other reasons that might prevent an individual from completing the study
8. If female, currently pregnant or breastfeeding, or planning on conception
9. Body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX (e.g., BMI > 40, excess fat tissue over the buttocks, emaciation).

• Primary Phenotype: Opioid-Related Disorders
• Buprenorphine, Naloxone Drug
• Naltrexone / administration and dosage

• OPRK1
• OPRM1
• PDYN

• Principal Investigator
  • John Rotrosen, MD. NYU Grossman School of Medicine, New York, NY, USA.
• Co-Principal Investigators
  • Joshua Lee, MD, Msc. NYU Grossman School of Medicine, New York, NY, USA.
  • Edward Nunes, MD. NY State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, New York, NY, USA.
• Funding Source
  • U10 DA013046; UG1/U10 DA013035. National Institutes of Health, Bethesda, MD, USA.