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Taking people in United StatesPhase 4

A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder

Key facts

Who runs it
VA Office of Research and Development
Where
Bay Pines, Boston, Cleveland, Dallas, Dayton, Gainesville, Hampton, Huntington, Long Beach, Milwaukee, Minneapolis, Palo Alto, Philadelphia, Phoenix, Pittsburgh, Providence, Salem, Salt Lake City, San Francisco, Seattle, Tuscaloosa, West Haven, White River Junction, and Wilmington, United StatesSee the 25 sites
Trial code
Status
Recruiting
Phase
Phase 4
People taking part
952 people, planned
Started
3 Nov 2020
Expected to end
31 May 2029
Type of study
Interventional, 2 groups
Treatments tested
  • Sublingual buprenorphine with naloxone
  • Injectable subcutaneous buprenorphine
Record updated
10 September 2026

Who can take part

Age
18 years and older
Sex
Women and men
Healthy volunteers
Cannot take part

The registry criteria, word for word

Show all 15 criteriaShow less

Who can take part

  • 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 take part

  • 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
  • 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
  • Has a history of significant adverse effects from buprenorphine and/or naloxone
  • 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
  • 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
  • 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
  • Anuria and/or dialysis
  • Is actively participating in an interventional clinical trial for which a waiver of dual-enrollment with CSP #2014 has not been obtained

Where in United States

  • Bay Pines VA Healthcare System, Pay Pines, FLBay Pines, United StatesContact: Maha Lahoud-Bladykas, MDTaking people
  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MABoston, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • Louis Stokes VA Medical Center, Cleveland, OHCleveland, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TXDallas, United StatesContact: Ashley Woolbert, MDTaking people
  • Dayton VA Medical Center, Dayton, OHDayton, United StatesContact: Bret Becker, MDTaking people
  • North Florida/South Georgia Veterans Health System, Gainesville, FLGainesville, United StatesContact: Leonardo Rodriguez, MDTaking people
  • Hampton VA Medical Center, Hampton, VAHampton, United StatesContact: Ajay Manhapra, MDTaking people
  • Huntington VA Medical Center, Huntington, WVHuntington, United StatesContact: Jack Wang, MDTaking people
  • VA Long Beach Healthcare System, Long Beach, CALong Beach, United StatesContact: Ricardo Restrepo-Guzman, MDTaking people
  • Clement J. Zablocki VA Medical Center, Milwaukee, WIMilwaukee, United StatesContact: Matthew Stohs, MDTaking people
  • Minneapolis VA Health Care System, Minneapolis, MNMinneapolis, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • VA Palo Alto Health Care System, Palo Alto, CAPalo Alto, United StatesContact: Michael Ostacher, MDTaking people
  • Philadelphia MultiService Center, Philadelphia, PAPhiladelphia, United StatesContact: Kyle Kampman, MDTaking people
  • Phoenix VA Health Care System, Phoenix, AZPhoenix, United StatesContact: Kerri Grover, BSNTaking people
  • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PAPittsburgh, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • Providence VA Medical Center, Providence, RIProvidence, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • Salem VA Medical Center, Salem, VASalem, United StatesContact: Anjali Varma, MDTaking people
  • VA Salt Lake City Health Care System, Salt Lake City, UTSalt Lake City, United StatesContact: Adam Gordon, MDTaking people
  • San Francisco VA Medical Center, San Francisco, CASan Francisco, United StatesContact: Steven Batki, MDTaking people
  • VA Puget Sound Health Care System Seattle Division, Seattle, WASeattle, United StatesContact: Justin Stamschror, MDTaking people
  • Tuscaloosa VA Medical Center, Tuscaloosa, ALTuscaloosa, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • CERC (VISN1, West Haven, CT)West Haven, United StatesContact: Brian Fuehrlein, MDTaking people
  • VA Connecticut Healthcare System West Haven Campus, West Haven, CTWest Haven, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • White River Junction VA Medical Center, White River Junction, VTWhite River Junction, United StatesContact: Avron Spiro, PhD MSNo longer taking part
  • Wilmington VA Medical Center, Wilmington, DEWilmington, United StatesContact: Daniel J LacheTaking people

About the trial

What the trial wants to find out

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.

The 2 groups in the trial

  • Sublingual ArmTreatment being tested

    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.

    Treatment: Sublingual buprenorphine with naloxone

  • Injectable ArmTreatment being tested

    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.

    Treatment: Injectable subcutaneous buprenorphine

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE)
Publications
Record updated
10 September 2026