A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder
Purpose
VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous (in the belly area) formulation of buprenorphine at a target dose of 300mg is superior in retaining Veterans in opioid treatment and in sustaining opioid abstinence compared to the daily sublingual (under the tongue) buprenorphine formulation at a target dose of 16-32 mg (standard of care). This is an open-label, randomized, controlled trial including 952 Veterans with opioid use disorder (OUD) recruited over 7 years and followed actively for 52 weeks. There are a number of secondary objectives that will be studied as well and include: comorbid substance use, both non-fatal and fatal opioid overdose, HIV and Hepatitis B (HBV) and C (HCV) testing results and risk behaviors, incarceration, quality of life, psychiatric symptoms of depression and posttraumatic stress disorder, housing status, dental health and utilization, and cost-effectiveness.
Condition
- Opioid Use Disorder
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Has used opioids within 30 days prior to consent or within 30 days prior to entry into a supervised setting -- e.g., opioid use within the 30 days prior to recent (<30 days) incarceration, entry into a detoxification facility, or entry into an inpatient hospital setting - Have started on MOUD via clinical induction on SL-BUP/NLX - Meets DSM-5 criteria for moderate to severe OUD based on the Mini-International Neuropsychiatric Interview - Referred to/seeking treatment for OUD and willing to accept "partial-agonist-based" therapy
Exclusion Criteria
- Is a Veteran less than 18 years of age - For Veterans of childbearing potential (a premenopausal person capable of becoming pregnant), pregnancy, breastfeeding, and/or failure to practice an effective method of birth control - Failure to reach maintenance dose of 8mg - 32mg SL-BUP/NLX in 45 days or less (must have taken 3 consecutive days of maintenance dose immediately before randomization). - Taking a form of prescribed maintenance MOUD (e.g., methadone, buprenorphine or XR-NTX) continuously >45 days prior to randomization - Has a history of significant adverse effects from buprenorphine and/or naloxone - Has experienced (within the past 2 weeks) recent suicidal or homicidal ideation that requires acute treatment or hospitalization. - Is unwilling or unable to provide consent - Meets criteria for current (past month) DSM-5 severe sedative hypnotic use disorder based on the MINI SHUD module - Anuria and/or dialysis - Current moderate to severe COVID-19 symptoms with a risk of intubation or critical illness. - Medical, psychiatric, behavioral, or logistical condition which, in the judgement of the Local Site Investigator (LSI) or Co-Investigator (Co-I), requires a higher level of acute care and/or makes it unlikely the patient can participate in or complete the 52-week active phase of the study. - Is actively participating in an interventional clinical trial for which a waiver of dual-enrollment with CSP #2014 has not been obtained.
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants are randomized 1:1 and assigned to receive at each 28-day research visit either: 1) a 28-day take-home supply of SL buprenorphine, prescribed at the clinically determined dose, or 2) injectable sub-cutaneous buprenorphine administered in the clinic (target dose = 300mg; 100mg dose may be used for those who cannot tolerate 300mg).
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Sublingual Arm |
The sublingual buprenorphine contains naloxone in a ratio of 4:1 and will be prescribed. Consistent with the SAMHSA guidelines, before SL-BUP/NLX is prescribed, participants will be evaluated for recent (within 24 hours) drug use and associated symptoms. The randomization dose will be determined based on the maintenance dose identified during the induction period, with a target dose of 16-32mg that is standard practice. While the target dose is 16-32mg, doses may go as low as 8mg as occasionally patients prefer lower doses. SL-BUP/NLX will be prescribed at the randomization visit (28-day supply), then every 4 weeks through week 48. |
|
|
Experimental Injectable Arm |
Injectable buprenorphine consists of a depot injectable formulation in polymeric solution and releases buprenorphine over a 28-day (4-week) period by diffusion as the polymer biodegrades. The injection will be administered subcutaneously in the abdomen at each 28-day visit. The target dose is 300mg, there is the option to use 100mg dose. The final study dose of injectable buprenorphine will be given at Week 48. |
|
Recruiting Locations
Phoenix, Arizona 85012
Long Beach, California 90822
Palo Alto, California 94304-1207
San Francisco, California 94121-1563
West Haven, Connecticut 06516-2770
Wilmington, Delaware 19805-4917
Bay Pines, Florida 33744-0000
Gainesville, Florida 32608-1135
Minneapolis, Minnesota 55417-2309
Dayton, Ohio 45428
Philadelphia, Pennsylvania 19106
Dallas, Texas 75216-7167
Salt Lake City, Utah 84148-0001
Hampton, Virginia 23667
Salem, Virginia 24153-6404
Seattle, Washington 98108-1532
Milwaukee, Wisconsin 53295-0001
More Details
- NCT ID
- NCT04375033
- Status
- Recruiting
- Sponsor
- VA Office of Research and Development
Detailed Description
CSP2014 is the first direct long-term comparison of monthly injectable versus daily SL buprenorphine. In addition to its impact on the care of Veterans, the results of VA-BRAVE will provide critical data to guide effective treatment of opioid use disorder throughout the United States. The CSP2014 study population is Veterans aged 18 years diagnosed with moderate to severe opioid use disorder (OUD) by Diagnostic and Statistical Manual (DSM)-5th edition criteria. Veterans must be entering a new episode of opioid use disorder care prior to study start. There are two primary outcomes that address key Veterans Health Administration (VHA) clinical issues related to opioid use disorder treatment. The first is retention on protocol-directed medication treatment (sublingual or injectable sub-cutaneous buprenorphine). The second primary outcome is opioid abstinence using the systematic Timeline Followback method of self-report and corresponding urine toxicology screens. VA-BRAVE includes a 52-week intervention with multiple study visits and up to a 10-year passive follow-up for the duration of the study. Participants are inducted on daily SL buprenorphine using SAMHSA guidelines and dosed upward for a target dose of 16-32 mg for 3 days (more than 3 days may be required if deemed clinically necessary; should not exceed 45 days). Once target dose reached, participants are randomized 1:1 and assigned to receive at each 28-day research visit either: 1) a 28-day take-home supply of SL buprenorphine, prescribed at the clinically determined dose, or 2) injectable sub-cutaneous buprenorphine administered in the clinic (target dose = 300mg; 100mg dose may be used for those who cannot tolerate 300mg). Participants also receive Medication Management intervention at these visits. Study visits for all participants occur at Weeks 1, 2, 3 and 4 post-randomization, and biweekly thereafter through Week 52. Self-reported abstinence and urine toxicology screens are obtained at biweekly visits. Following one year of active follow-up, administrative data will be used to follow participants for up to 10 years for early enrollees and up to 7 years for late enrollees. The recruitment expectation is 7 new participants per study year per study site. There will be up to 20 participating VA Medical Center sites.