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

NCT ID: NCT04375033

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

952 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-03

Study Completion Date

2029-05-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Opioid Use Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Sublingual buprenorphine with naloxone

Intervention Type DRUG

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 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.

Group Type EXPERIMENTAL

Injectable subcutaneous buprenorphine

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are 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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ismene L. Petrakis, MD

Role: STUDY_CHAIR

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Sandra Ann Springer, MD

Role: STUDY_CHAIR

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Tuscaloosa, Alabama, United States

Site Status TERMINATED

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, United States

Site Status RECRUITING

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status RECRUITING

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

Site Status RECRUITING

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

Site Status RECRUITING

CERC (VISN1, West Haven, CT)

West Haven, Connecticut, United States

Site Status RECRUITING

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, United States

Site Status ACTIVE_NOT_RECRUITING

Wilmington VA Medical Center, Wilmington, DE

Wilmington, Delaware, United States

Site Status RECRUITING

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, United States

Site Status RECRUITING

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

Gainesville, Florida, United States

Site Status RECRUITING

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Site Status TERMINATED

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Site Status TERMINATED

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Site Status TERMINATED

Dayton VA Medical Center, Dayton, OH

Dayton, Ohio, United States

Site Status RECRUITING

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States

Site Status TERMINATED

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, United States

Site Status TERMINATED

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

Dallas, Texas, United States

Site Status RECRUITING

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

Salt Lake City, Utah, United States

Site Status RECRUITING

White River Junction VA Medical Center, White River Junction, VT

White River Junction, Vermont, United States

Site Status TERMINATED

Hampton VA Medical Center, Hampton, VA

Hampton, Virginia, United States

Site Status RECRUITING

Salem VA Medical Center, Salem, VA

Salem, Virginia, United States

Site Status RECRUITING

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

Seattle, Washington, United States

Site Status RECRUITING

Huntington VA Medical Center, Huntington, WV

Huntington, West Virginia, United States

Site Status NOT_YET_RECRUITING

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Avron Spiro, PhD MS

Role: CONTACT

(857) 364-2888

Melynn Nuite, RN BS CCRC

Role: CONTACT

(617) 232-9500

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Kerri Grover, BSN

Role: primary

602-277-5551 ext. 2436

Ricardo Restrepo-Guzman, MD

Role: primary

Aliya Uddin, MPH

Role: backup

5628265212

Michael Ostacher, MD

Role: primary

Edgardo Gamarra Monteverde, MPH

Role: backup

6504935000 ext. 63266

Steven Batki, MD

Role: primary

Alexander Kinzler

Role: backup

Brian Fuehrlein, MD

Role: primary

James Silas

Role: backup

2039325711

Daniel J Lache

Role: primary

Christen Holmes

Role: backup

2158235800 ext. 3404

Maha Lahoud-Bladykas, MD

Role: primary

Christopher Vallanat

Role: backup

7273986661 ext. 15568

Leonardo Rodriguez, MD

Role: primary

Terrill (Tee) Byrd, NP

Role: backup

3523761611 ext. 104597

Bret Becker, MD

Role: primary

TJ Exford, PhD

Role: backup

9372686511 ext. 1202

Kyle Kampman, MD

Role: primary

Christen Holmes

Role: backup

2158235800 ext. 3404

Ashley Woolbert, MD

Role: primary

Brandy Brown, RN

Role: backup

2148571014

Adam Gordon, MD

Role: primary

Lamb Miranda, RN

Role: backup

8015821565 ext. 2733

Ajay Manhapra, MD

Role: primary

757-722-9961 ext. 5916

Maria Levasseur, MPH

Role: backup

7577229961 ext. 6061

Anjali Varma, MD

Role: primary

Brian Beverly

Role: backup

(540) 2241914

Justin Stamschror, MD

Role: primary

Michael Emery, PhD

Role: backup

2067642283

Jack Wang, MD

Role: primary

Jake Cogan

Role: backup

3044296741 ext. 3804

Matthew Stohs, MD

Role: primary

Joe Berman

Role: backup

4143842000 ext. 46386

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 35101115 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Buprenorphine Naltrexone-P1 A-Cocaine
NCT00733720 COMPLETED PHASE1
Injectable Buprenorphine in Prison: a Preference Trial
NCT06880718 NOT_YET_RECRUITING PHASE4