Comparing Monthly Injectable vs Daily Oral Buprenorphine for Treating Opioid Use Disorder in Veterans
A Phase 4 Study of Two Buprenorphine Treatments Over One Year
Led by VA Office of Research and Development · Updated on 2026-01-12
952
Participants Needed
25
Research Sites
34 weeks
Total Duration
AI-Summary
What this Trial Is About
Researchers are evaluating the effectiveness of a long-acting injectable form of buprenorphine compared to the daily sublingual under the tongue buprenorphine in treating Veterans with moderate to severe opioid use disorder OUD. This open-label, randomized controlled trial aims to see which treatment better retains Veterans in opioid therapy and helps sustain opioid abstinence. The study also examines secondary outcomes such as substance use, overdose incidents, infectious disease testing, psychiatric symptoms, housing status, dental health, and cost-effectiveness.
Participants are Veterans aged 18 and older diagnosed with moderate to severe OUD and beginning a new treatment episode. After an induction period on daily sublingual buprenorphine, participants are randomly assigned to receive either a 28-day supply of daily sublingual buprenorphine or a monthly injectable buprenorphine shot administered in the clinic. Doses for the injectable form target 300mg, with a 100mg option for those who cannot tolerate the higher dose. Study visits occur weekly during the first month, then every two weeks until week 52, including medication management.
Throughout the 52-week active phase, participants report opioid use and provide urine samples every two weeks to evaluate abstinence and treatment retention. Additional assessments include HIV, Hepatitis B and C testing, psychiatric questionnaires, risk behavior evaluations, and dental health surveys. After the active phase, participants are followed passively using medical records for up to 10 years to monitor long-term outcomes. The study expects to recruit 952 Veterans over 7 years across multiple VA Medical Centers.
CONDITIONS
Brief Title
A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder
Research Team
A
Avron Spiro, PhD MS
M
Melynn Nuite, RN BS CCRC
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This table compares participation in this trial with other options available for this condition. The information is drawn from published research and the trial’s study details and is provided for educational purposes only.
A monthly biodegradable subcutaneous depot injection releasing buprenorphine over 28 days, administered every 28 days up to week 48
A once‑daily oral sublingual combination of buprenorphine and naloxone supplied for 28‑day coverage at each visit through week 48
Daily sublingual buprenorphine‑naloxone is widely used as standard medication for OUD treatment
Role in trial
Investigational arm being evaluated for retention and abstinence
Active control comparator arm following current induction on sublingual buprenorphine/naloxone
Represents guideline‑recommended OUD treatment in routine care
Purpose or use
Maintaining opioid abstinence and treatment retention with less frequent dosing
Daily opioid use disorder maintenance therapy with buprenorphine and naloxone
Daily maintenance therapy for OUD based on clear clinical evidence and practice
Administration
Depot injection under the skin every 28 days
Daily sublingual film or tablet dispensed for daily self‑administration
Prescribed daily sublingual dose taken by the patient every day
Evidence status
Effectiveness under investigation in this trial; limited prior data on retention or abstinence advantage
Established efficacy in reducing opioid use and promoting retention
Strong evidence supports its effectiveness in everyday clinical use
Important risks
Potential injection‑site reactions and limited long‑term safety data
Risks include diversion, misuse, and potential partial agonist side effects
Known safety profile with risks managed in routine care
Important limitations
Study assesses only retention and abstinence without cost‑effectiveness or preference data
Requires daily adherence and may be subject to misuse or diversion
Daily dosing may challenge adherence in some patients
Patient impact
Potential for reduced dosing burden and improved retention, though not yet proven
Proven to reduce opioid use and improve retention when taken daily
Daily sublingual buprenorphine leads to better outcomes compared to no treatment
Disclaimer: This comparison is created with the help of artificial intelligence(AI) and may contain errors or missing information. It is not medical advice and does not mean one option is better or safer than another. Clinical trials are still being studied, and joining a trial is your choice. Please consult your healthcare professional before making any decisions.
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
Has used opioids within 30 days prior to consent or prior to entry into a supervised setting
Have started or are in the process of starting medication treatment with sublingual buprenorphine with naloxone
Meets DSM-5 criteria for moderate to severe opioid use disorder
Referred to or seeking treatment for opioid use disorder and willing to accept partial-agonist-based therapy
Aged 18 years or older
You will not qualify if you...
Is a Veteran younger than 18 years
Pregnancy, breastfeeding, or not using effective birth control for those of childbearing potential
Failure to reach maintenance dose of 4mg to 32mg sublingual buprenorphine with naloxone within 45 days
Taking maintenance medication for opioid use disorder continuously for more than 45 days prior to randomization
History of significant adverse effects from buprenorphine or naloxone
Recent suicidal or homicidal ideation requiring acute treatment or hospitalization
Unwilling or unable to provide consent
Current severe sedative hypnotic use disorder
Anuria or dialysis
Moderate to severe COVID-19 symptoms with risk of critical illness
Medical, psychiatric, behavioral, or logistical conditions preventing participation or completion of the 52-week study
Actively enrolled in another interventional clinical trial without waiver of dual enrollment
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) to assess eligibility and start induction
Run-in Period
Duration - Up to 45 days
Participants start daily sublingual buprenorphine induction and dose titration to reach maintenance dose before randomization.
Weekly visits for up to 6 weeks during induction
Treatment
Duration - 52 weeks
Participants receive either daily oral sublingual buprenorphine or monthly injectable subcutaneous buprenorphine along with medication management.
Visits at Weeks 1, 2, 3, and 4 post-randomization, then biweekly visits through Week 52
Follow-up
Duration - Up to 10 years
Participants are passively followed through administrative data for up to 10 years after active treatment ends.
No in-person visits; data collected via electronic medical records
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Published Research Related To This Trial
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.
Ismene Petrakis, Sandra A Springer, Cynthia Davis...