Recruiting

Oral & Injectable Buprenorphine

Sponsor:

VA Office of Research and Development

Code:

NCT04375033

Conditions

Opioid Use Disorder

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sublingual buprenorphine with naloxone

Injectable subcutaneous buprenorphine

Study Details

Brief summary:

VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous 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 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.

Conditions

Opioid Use Disorder

Study ID

NCT04375033

Start date

Nov 3, 2020

Status verified date

Jan, 2026

Completion date

May 31, 2029

Anticipated

Primary completion date

Sep 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 or are in the process of starting 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
  • Veteran status confirmed: participant must have served in the U.S. Armed Forces

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 4mg - 32mg SL-BUP/NLX in 45 days or less.
  • 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

Enrollment

952 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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 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.

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 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.

Interventions

Sublingual buprenorphine with naloxone

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 buprenorphine

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.

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 ]
  • Opioid Abstinence [ Time Frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase) ]

Central Contacts and Locations

Central contacts

Avron Spiro, PhD MS

(857) 364-2888avron.spiro@va.gov

Melynn Nuite, RN BS CCRC

(617) 232-9500Melynn.Nuite@va.gov

Locations

Phoenix VA Health Care System, Phoenix, AZ

Recruiting

Phoenix, Arizona, United States, 85012

Contacts

Kerri Grover, BSN

602-277-5551kerri.grover@va.gov

VA Long Beach Healthcare System, Long Beach, CA

Recruiting

Long Beach, California, United States, 90822

Contacts

Ricardo Restrepo-Guzman, MD

ricardo.restrepo-guzman@va.gov

Aliya Uddin, MPH

5628265212aliya.uddin@va.gov

VA Palo Alto Health Care System, Palo Alto, CA

Recruiting

Palo Alto, California, United States, 94304-1207

Contacts

Michael Ostacher, MD

michael.ostacher@va.gov

Edgardo Gamarra Monteverde, MPH

6504935000edgardo.gamarramonteverde@va.gov

San Francisco VA Medical Center, San Francisco, CA

Recruiting

San Francisco, California, United States, 94121-1563

Contacts

Steven Batki, MD

steven.batki@va.gov

Alexander Kinzler

alexander.kinzler@va.gov

CERC (VISN1, West Haven, CT)

Recruiting

West Haven, Connecticut, United States, 06516-2770

Contacts

Brian Fuehrlein, MD

brian.fuehrlein@va.gov

James Silas

2039325711james.silas@va.gov

Wilmington VA Medical Center, Wilmington, DE

Recruiting

Wilmington, Delaware, United States, 19805-4917

Contacts

Daniel J Lache

daniel.lache2@va.gov

Christen Holmes

2158235800christen.holmes2@va.gov

Bay Pines VA Healthcare System, Pay Pines, FL

Recruiting

Bay Pines, Florida, United States, 33744-0000

Contacts

Maha Lahoud-Bladykas, MD

maha.lahoud-bladykas@va.gov

Christopher Vallanat

7273986661Christopher.Vallanat@va.gov

North Florida/South Georgia Veterans Health System, Gainesville, FL

Recruiting

Gainesville, Florida, United States, 32608-1135

Contacts

Leonardo Rodriguez, MD

leonardo.rodriguez@va.gov

Terrill (Tee) Byrd, NP

3523761611terrill.byrd@va.gov

Dayton VA Medical Center, Dayton, OH

Recruiting

Dayton, Ohio, United States, 45428

Contacts

Bret Becker, MD

bret.becker@va.gov

TJ Exford, PhD

9372686511tj.exford@va.gov

Philadelphia MultiService Center, Philadelphia, PA

Recruiting

Philadelphia, Pennsylvania, United States, 19106

Contacts

Kyle Kampman, MD

kyle.kampman@va.gov

Christen Holmes

2158235800christen.holmes2@va.gov

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Recruiting

Dallas, Texas, United States, 75216-7167

Contacts

Ashley Woolbert, MD

ashley.woolbert@va.gov

Brandy Brown, RN

2148571014brandy.brown3@va.gov

VA Salt Lake City Health Care System, Salt Lake City, UT

Recruiting

Salt Lake City, Utah, United States, 84148-0001

Contacts

Adam Gordon, MD

adam.gordon@va.gov

Lamb Miranda, RN

8015821565miranda.lamb@va.gov

Hampton VA Medical Center, Hampton, VA

Recruiting

Hampton, Virginia, United States, 23667

Contacts

Ajay Manhapra, MD

757-722-9961ajay.manhapra@va.gov

Maria Levasseur, MPH

7577229961maria.levasseur@va.gov

Salem VA Medical Center, Salem, VA

Recruiting

Salem, Virginia, United States, 24153-6404

Contacts

Anjali Varma, MD

anjali.varma@va.gov

Brian Beverly

(540) 2241914brian.beverly2@va.gov

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Recruiting

Seattle, Washington, United States, 98108-1532

Contacts

Justin Stamschror, MD

justin.stamschror@va.gov

Michael Emery, PhD

2067642283michael.emery2@va.gov

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Recruiting

Milwaukee, Wisconsin, United States, 53295-0001

Contacts

Matthew Stohs, MD

matthew.stohs@va.gov

Joe Berman

4143842000joe.berman@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Jan 12, 2026

Last verified

Jan, 2026

Keywords

  • Buprenorphine
  • Veterans
  • Clinical Trial
  • Opioid Abstinence
  • Retention in Care
  • Pharmacotherapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-03. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-01-12. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.