This pilot trial will explore the feasibility, acceptability, and effectiveness of the most recently approved formulation of injectable extended-release buprenorphine (XR-BUP) for treatment of opioid use disorder (OUD) in rural settings. We will randomize 144 eligible individuals with moderate to severe OUD in a 2:1 ratio to one of two medication conditions: (1) XR-BUP (128mg target), administered every 4 weeks or (2) SL-BUP (16mg-24 mg/day target).Participants will receive study medication treatment for the 14 week-intervention period, including an initial ~2-week period of induction/stabilization. The study will use a mixed-methods approach (participant assessments, study medication records, qualitative interviews) for assessing feasibility and acceptability, and results will include patient outcome data on the comparative effectiveness of XR-BUP versus SL-BUP for patients with OUD in rural settings.

This 24-month randomized controlled open-label pilot study will be conducted in approximately 6 clinics in rural settings. The study objectives are to describe the feasibility of implementing the study in rural settings, document the acceptability of the XR-BUP condition, and assess the comparative effectiveness of XR-BUP compared with SL-BUP. Participants will be randomized within each clinic to XR-BUP or SL-BUP in a ratio of 2:1 (overall approximately 96 in the XR-BUP condition, 48 in the SL-BUP condition). They will receive study medication for approximately 14 weeks following randomization, including an initial ~2-week period of induction/stabilization. The XR-BUP condition will use Brixadi®/CAM2038 injectable, extended-release buprenorphine. The measure for the main comparative effectiveness outcome is number of urine drug screen (UDS) results negative for opioids at scheduled assessments during Week 2 through Week 14 of the trial. Missing or positive UDS for any non-prescribed opioid is considered UDS positive.

Inclusion Criteria:

1. Be ≥18 years of age
2. Meet DSM-5 criteria for moderate to severe OUD or be on buprenorphine medication for OUD
3. Be interested in receiving buprenorphine treatment for OUD
4. Be willing to be randomized to either SL-BUP or XR-BUP
5. Be willing to comply with all study procedures
6. Be in good general health, as determined by the study Medical Clinician based on medical/psychiatric histories and physical exam, to permit treatment in an outpatient setting
7. If female of childbearing potential, be willing to practice an effective method of birth control for the duration of participation in the study intervention and agree to study-administered pregnancy testing during their participation in the study
8. Be able to speak English sufficiently to understand the study procedures
9. Be willing and able to provide written informed consent to participate in the study

Exclusion Criteria:

1. Have evidence of a serious psychiatric disorder as assessed by the study Medical Clinician that would make participation difficult or unsafe (e.g., active psychosis, severe depression, or mania)
2. Have suicidal or homicidal ideation or behavior that requires immediate attention
3. Have a medical condition or serious medical illness that, in the opinion of the study Medical Clinician, would make study participation medically unsafe
4. Have been in treatment with naltrexone within 28 days of consent
5. Have been in methadone maintenance treatment within 28 days of consent
6. Be taking medication or require any medication that, in the judgment of the study Medical Clinician, could interact adversely with study medication
7. Have known allergy or sensitivity to SL-BUP or XR-BUP formulations or their components
8. Be currently incarcerated or have pending legal action that could preclude participation in study activities
9. Have other situation that might prevent the participant from remaining in the area for the duration of the study (e.g., planned move)
10. Have a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use, as determined by the study Medical Clinician, that would require a different level of care and preclude safe participation in the study
11. Be currently pregnant or breastfeeding or planning on conception

This study will comply with the NIH Data Sharing Policy and Implementation Guidance and the HEAL Public Access and Data Sharing Policy. Primary data for this study will be available to the public in the NIDA Data Share repository, per NIDA CTN policy. For more details on data sharing please visit https://datashare.nida.nih.gov/.The main outcome(s) publication will be included along with study underlying primary data in the data share repository, and it will also be deposited in PubMed Central http://www.pubmedcentral.nih.gov/ per NIH Policy (http://publicaccess.nih.gov/).

After the main outcome(s) paper(s) have been published or 18 months after data lock, whichever comes first.

For more details on data sharing please visit https://datashare.nida.nih.gov