Opioid Use DisorderPhase 4VA-BRAVENCT04375033
A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder
A Phase 4 study testing Sublingual buprenorphine with naloxone and Injectable subcutaneous buprenorphine in people with Opioid Use Disorder, run by VA Office of Research and Development at 25 sites in United States.
Trial summary
VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous formulation of buprenorphine at a target dose of 300 milligrams (mg) 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Sublingual buprenorphine with naloxone and Injectable subcutaneous buprenorphine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 952 participants
- Where
- 25 sitesUnited States
- Study dates
- 3 Nov 2020to 31 May 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 or are in the process of starting on Medications for Opioid Use Disorder (MOUD) via clinical induction on SL-BUP/NLX
- Meets DSM-5 criteria for moderate to severe opioid use disorder (OUD) based on the Mini-International Neuropsychiatric Interview
- Referred to/seeking treatment for OUD and willing to accept "partial-agonist-based" therapy
Who cannot join
- 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 4 milligrams (mg) - 32mg SL-BUP/NLX in 45 days or less
- Taking a form of prescribed maintenance Medications for Opioid Use Disorder (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
Show all 11Show fewer
- Meets criteria for current (past month) DSM-5 severe sedative hypnotic use disorder based on the MINI Sedative, Hypnotic, or Anxiolytic Use Disorder (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
Trial locations and contacts
25 sites in 1 country. Contact the study team or a site near you to ask about taking part.
25 sites in 1 country
United States25 sites, 17 recruiting
- Recruiting
Bay Pines VA Healthcare System, Pay Pines, FL
Bay Pines, Florida, 33744-0000
Maha Lahoud-Bladykas, MD, maha.lahoud-bladykas@va.gov
Christopher Vallanat, 7273986661 ext. 15568, Christopher.Vallanat@va.gov
- Terminated
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130
- Terminated
Louis Stokes VA Medical Center, Cleveland, OH
Cleveland, Ohio, 44106
- Recruiting
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216-7167
Ashley Woolbert, MD, ashley.woolbert@va.gov
Brandy Brown, RN, 2148571014, brandy.brown3@va.gov
- Recruiting
Dayton VA Medical Center, Dayton, OH
Dayton, Ohio, 45428
Bret Becker, MD, bret.becker@va.gov
TJ Exford, PhD, 9372686511 ext. 1202, tj.exford@va.gov
- Recruiting
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, 32608-1135
Leonardo Rodriguez, MD, leonardo.rodriguez@va.gov
Terrill (Tee) Byrd, NP, 3523761611 ext. 104597, terrill.byrd@va.gov
- Recruiting
Hampton VA Medical Center, Hampton, VA
Hampton, Virginia, 23667
Ajay Manhapra, MD, 757-722-9961 ext. 5916, ajay.manhapra@va.gov
Maria Levasseur, MPH, 7577229961 ext. 6061, maria.levasseur@va.gov
- Recruiting
Huntington VA Medical Center, Huntington, WV
Huntington, West Virginia, 25704-9300
Jack Wang, MD, jack.wang@va.gov
Heather Pelfrey, RN, 3044296741 ext. 3802, heather.pelfrey@va.gov
- Recruiting
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, 90822
Ricardo Restrepo-Guzman, MD, ricardo.restrepo-guzman@va.gov
Aliya Uddin, MPH, 5628265212, aliya.uddin@va.gov
- Recruiting
Clement J. Zablocki VA Medical Center, Milwaukee, WI
Milwaukee, Wisconsin, 53295-0001
Matthew Stohs, MD, matthew.stohs@va.gov
Joe Berman, 4143842000 ext. 46386, joe.berman@va.gov
- Terminated
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309
- Recruiting
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1207
Michael Ostacher, MD, michael.ostacher@va.gov
Edgardo Gamarra Monteverde, MPH, 6504935000 ext. 63266, edgardo.gamarramonteverde@va.gov
- Recruiting
Philadelphia MultiService Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19106
Kyle Kampman, MD, kyle.kampman@va.gov
Christen Holmes, 2158235800 ext. 3404, christen.holmes2@va.gov
- Recruiting
Phoenix VA Health Care System, Phoenix, AZ
Phoenix, Arizona, 85012
Kerri Grover, BSN, 602-277-5551 ext. 2436, kerri.grover@va.gov
- Terminated
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240
- Terminated
Providence VA Medical Center, Providence, RI
Providence, Rhode Island, 02908-4734
- Recruiting
Salem VA Medical Center, Salem, VA
Salem, Virginia, 24153-6404
Anjali Varma, MD, anjali.varma@va.gov
Brian Beverly, (540) 2241914, brian.beverly2@va.gov
- Recruiting
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001
Adam Gordon, MD, adam.gordon@va.gov
Lamb Miranda, RN, 8015821565 ext. 2733, miranda.lamb@va.gov
- Recruiting
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121-1563
Steven Batki, MD, steven.batki@va.gov
Alexander Kinzler, alexander.kinzler@va.gov
- Recruiting
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532
Justin Stamschror, MD, justin.stamschror@va.gov
Michael Emery, PhD, 2067642283, michael.emery2@va.gov
- Terminated
Tuscaloosa VA Medical Center, Tuscaloosa, AL
Tuscaloosa, Alabama, 35404-5015
- Recruiting
CERC (VISN1, West Haven, CT)
West Haven, Connecticut, 06516-2770
Brian Fuehrlein, MD, brian.fuehrlein@va.gov
James Silas, 2039325711, james.silas@va.gov
- Active, not recruiting
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516-2770
- Terminated
White River Junction VA Medical Center, White River Junction, VT
White River Junction, Vermont, 05001-3833
- Recruiting
Wilmington VA Medical Center, Wilmington, DE
Wilmington, Delaware, 19805-4917
Daniel J Lache, daniel.lache2@va.gov
Christen Holmes, 2158235800 ext. 3404, christen.holmes2@va.gov
About this study
Official title: CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE)
VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous formulation of buprenorphine at a target dose of 300 milligrams (mg) 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 4-32 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.
Read the 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 4-32 mg for 1 day (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.
- Conditions
- Opioid Use Disorder
- Being tested
- Sublingual buprenorphine with naloxone, Injectable subcutaneous buprenorphine
- Keywords
- Buprenorphine, Veterans, Clinical Trial, Opioid Abstinence, Retention in Care, Pharmacotherapy
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sublingual buprenorphine with naloxoneDrug
The combination SL-containing buprenorphine contains naloxone in a ratio of 4:1 buprenorphine:naloxone. Participants will be given a 28-prescription at each 28-day visit through Week 48.
Injectable subcutaneous buprenorphineDrug
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 at each 28-day visit through Week 48.
| Study group | Role | What they receive |
|---|---|---|
| Sublingual Arm | Experimental | 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 4-32mg that is standard practice. While the target dose is 4-32mg, occasionally patients may prefer lower doses. SL-BUP/NLX will be prescribed at the randomization visit (28-day supply), then every 4 weeks through week 48. Receives: Drug: Sublingual buprenorphine with naloxone |
| Injectable Arm | Experimental | 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 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. Receives: Drug: Injectable subcutaneous buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retention in Treatment Change
Measured by receipt of prescribed study drug (via prescription or admission) and assessed via local study team records. Retention-in-treatment is a highly sensitive indicator of effective treatment as discontinuation is strongly associated with recurrence of use to opioids and risk for accidental drug poisoning.
Measured: Approximately every 4 weeks until the first period of missed prescription medication coverage lasting at least 4 weeks through week 52
Opioid Abstinence
Measured by Timeline Followback (self-report measure of substance use) and urine toxicology free of opioids. Both Timeline Followback and urine toxicology must indicate non-use to indicate abstinence.
Measured: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Secondary outcomes (10)
Accidental Opioid Poisoning (overdose)
Self-reported non-fatal accidental opioid poisoning, hospital records, and CDC data on fatal accidental drug poisoning (by state) will be used to indicate fatal and non-fatal accidental opioid poisoning.
Measured: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) seroconversion
Assessment will indicate positive seroconversion for HIV, HBV, or HCV based on HIV-1 p24 antigen/antibody with reflex HIV RNA viral load, HBV sAB, sAG with reflex HBV viral load if HBV sAG positive only, and HCV AB with reflex HCV viral load. These tests are recommended as standard care for Veterans with OUD.
Measured: Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)
Healthcare and Service Utilization
An indicator of healthcare and service utilization will be obtained using the Service Utilization Review Form (SURF) that assesses utilization of VHA inpatient and outpatient care clinics, SUD clinics, detoxification programs, and pharmacies located within the VHA and local hospitals. Participants' use of other treatments will be documented on the SURF; non-VA health services will also be captured using the SURF.
Measured: Assess from baseline approximately every 4 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Other Addictive Substances
Measured by Timeline Followback (self-report measure of substance use) and urine toxicology free of other addictive substances. Both Timeline Followback and urine toxicology must indicate non-use to indicate abstinence.
Measured: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Opioid Craving
Opioid craving will be measured on a 10-point Likert scale in response to the question "Please indicate how much you are craving opioids right now."
Measured: Approximately every 4 weeks through 52 weeks (active phase)
HIV Sexual and Injection Risk Behaviors
HIV sexual and injection risk behaviors will be assessed using NIDA's HIV Risk Behavior tool.
Measured: Assessed at baseline, weeks 12, 24, 36, and 52
Patient Health Questionnaire (PHQ-9)
A measure of depressive symptoms (overall) and suicidality (item 9)
Measured: Assessed at baseline, weeks 12, 24, 36, and 52
Post-traumatic stress disorder (PTSD) Checklist for DSM-5
A measure of PTSD symptoms
Measured: Assessed at baseline, weeks 12, 24, 36, and 52
Texas Christian University Criminal Justice Form
A measure of incarceration, arrests, criminal activity.
Measured: Assessed at baseline, weeks 12, 24, 36, and 52
Dental Quality of Life Questionnaire
Self-report measure assessing oral/dental health and quality of life, salivary function, access to and use of dental healthcare.
Measured: Assessed at baseline, weeks 24 and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start3 Nov 2020
- Primary completion30 Sep 2028 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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).
- Masking
- None (open label)
- Enrolment
- 952 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ismene L. Petrakis, MD, Study chair, VA Connecticut Healthcare System West Haven Campus, West Haven, CTSandra Ann Springer, MD, Study chair, VA Connecticut Healthcare System West Haven Campus, West Haven, CT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04375033
- Sponsor's protocol ID
- 2014
- Acronym
- VA-BRAVE
- Status last verified
- Sep 2026
- First submitted
- 3 Apr 2020
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Petrakis I, Springer SA, Davis C, Ralevski E, Gu L, Lew R, Hermos J, Nuite M, Gordon AJ, Kosten TR, Nunes EV, Rosenheck R, Saxon AJ, Swift R, Goldberg A, Ringer R, Ferguson R. Rationale, design and methods of VA-BRAVE: a randomized comparative effectiveness trial of two formulations of buprenorphine for treatment of opioid use disorder in veterans. Addict Sci Clin Pract. 2022 Jan 31;17(1):6. doi: 10.1186/s13722-022-00286-6.
PubMed 35101115
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE)
- ClinicalTrials.gov ID
- NCT04375033
- Acronym / sponsor ID
- VA-BRAVE / 2014
- Conditions
- Opioid Use Disorder
- Keywords
- Buprenorphine, Veterans, Clinical Trial, Opioid Abstinence, Retention in Care, Pharmacotherapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 952 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 3 Nov 2020 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 5 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous formulation of buprenorphine at a target dose of 300 milligrams (mg) 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 4-32 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.
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 4-32 mg for 1 day (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Sublingual Arm | Experimental | Drug: Sublingual buprenorphine with naloxoneThe 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 4-32mg that is standard practice. While the target dose is 4-32mg, occasionally patients may prefer lower doses. SL-BUP/NLX will be prescribed at the randomization visit (28-day supply), then every 4 weeks through week 48. |
| Injectable Arm | Experimental | Drug: Injectable subcutaneous buprenorphineInjectable 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 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 or are in the process of starting on Medications for Opioid Use Disorder (MOUD) via clinical induction on SL-BUP/NLX
- Meets DSM-5 criteria for moderate to severe opioid use disorder (OUD) based on the Mini-International Neuropsychiatric Interview
- Referred to/seeking treatment for OUD and willing to accept "partial-agonist-based" therapy
Key exclusion criteria (11 listed)
- 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 4 milligrams (mg) - 32mg SL-BUP/NLX in 45 days or less
- Taking a form of prescribed maintenance Medications for Opioid Use Disorder (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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sublingual buprenorphine with naloxoneThe combination SL-containing buprenorphine contains naloxone in a ratio of 4:1 buprenorphine:naloxone. Participants will be given a 28-prescription at each 28-day visit through Week 48. | Drug | Sublingual Arm |
| Injectable subcutaneous buprenorphineInjectable 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 at each 28-day visit through Week 48. | Drug | Injectable Arm |
Primary outcome
Retention in Treatment Change
Time frame: Approximately every 4 weeks until the first period of missed prescription medication coverage lasting at least 4 weeks through week 52
Measured by receipt of prescribed study drug (via prescription or admission) and assessed via local study team records. Retention-in-treatment is a highly sensitive indicator of effective treatment as discontinuation is strongly associated with recurrence of use to opioids and risk for accidental drug poisoning.
Opioid Abstinence
Time frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Measured by Timeline Followback (self-report measure of substance use) and urine toxicology free of opioids. Both Timeline Followback and urine toxicology must indicate non-use to indicate abstinence.
10 secondary outcomes
Accidental Opioid Poisoning (overdose)
Time frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) seroconversion
Time frame: Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)
Healthcare and Service Utilization
Time frame: Assess from baseline approximately every 4 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Other Addictive Substances
Time frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Opioid Craving
Time frame: Approximately every 4 weeks through 52 weeks (active phase)
HIV Sexual and Injection Risk Behaviors
Time frame: Assessed at baseline, weeks 12, 24, 36, and 52
Patient Health Questionnaire (PHQ-9)
Time frame: Assessed at baseline, weeks 12, 24, 36, and 52
Post-traumatic stress disorder (PTSD) Checklist for DSM-5
Time frame: Assessed at baseline, weeks 12, 24, 36, and 52
Texas Christian University Criminal Justice Form
Time frame: Assessed at baseline, weeks 12, 24, 36, and 52
Dental Quality of Life Questionnaire
Time frame: Assessed at baseline, weeks 24 and 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Background: PubMed 35101115Petrakis I, Springer SA, Davis C, Ralevski E, Gu L, Lew R, Hermos J, Nuite M, Gordon AJ, Kosten TR, Nunes EV, Rosenheck R, Saxon AJ, Swift R, Goldberg A, Ringer R, Ferguson R. Rationale, design and methods of VA-BRAVE: a randomized comparative effectiveness trial of two formulations of buprenorphine for treatment of opioid use disorder in veterans. Addict Sci Clin Pract. 2022 Jan 31;17(1):6. doi: 10.1186/s13722-022-00286-6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ismene L. Petrakis, MD study chair
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
Sandra Ann Springer, MD study chair
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sublingual buprenorphine with naloxone and Injectable subcutaneous buprenorphine in people with Opioid Use Disorder, run by VA Office of Research and Development at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Avron Spiro, PhD MS ((857) 364-2888, avron.spiro@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Retention in Treatment Change (time frame: Approximately every 4 weeks until the first period of missed prescription medication coverage lasting at least 4 weeks through week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04375033, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.