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

NCT04375033 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2014
• Study Type: interventional
• Target: 952
• Locations: 1 country
• Sites: 25

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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

  Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)

• Healthcare and Service Utilization

  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

  Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)

• Opioid Craving

  Approximately every 4 weeks through 52 weeks (active phase)

Study Arms (2)

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.

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.

Drug: Injectable subcutaneous buprenorphine

Interventions

Sublingual buprenorphine with naloxone 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.

Sublingual Arm

Injectable subcutaneous buprenorphine 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.

Injectable Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (25)

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Tuscaloosa, Alabama, 35404-5015, United States

TERMINATED

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, 85012, United States

RECRUITING

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

RECRUITING

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1207, United States

RECRUITING

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121-1563, United States

RECRUITING

CERC (VISN1, West Haven, CT)

West Haven, Connecticut, 06516-2770, United States

RECRUITING

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

West Haven, Connecticut, 06516-2770, United States

ACTIVE NOT RECRUITING

Wilmington VA Medical Center, Wilmington, DE

Wilmington, Delaware, 19805-4917, United States

RECRUITING

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744-0000, United States

RECRUITING

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

Gainesville, Florida, 32608-1135, United States

RECRUITING

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

Boston, Massachusetts, 02130, United States

TERMINATED

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

TERMINATED

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

TERMINATED

Dayton VA Medical Center, Dayton, OH

Dayton, Ohio, 45428, United States

RECRUITING

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

TERMINATED

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734, United States

TERMINATED

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

Dallas, Texas, 75216-7167, United States

RECRUITING

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

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

RECRUITING

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

White River Junction, Vermont, 05001-3833, United States

TERMINATED

Hampton VA Medical Center, Hampton, VA

Hampton, Virginia, 23667, United States

RECRUITING

Salem VA Medical Center, Salem, VA

Salem, Virginia, 24153-6404, United States

RECRUITING

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

Seattle, Washington, 98108-1532, United States

RECRUITING

Huntington VA Medical Center, Huntington, WV

Huntington, West Virginia, 25704-9300, United States

NOT YET RECRUITING

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-0001, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 35101115 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Naloxone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Ismene L. Petrakis, MD

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

  STUDY CHAIR

• Sandra Ann Springer, MD

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

  STUDY CHAIR

Central Study Contacts

Avron Spiro, PhD MS

CONTACT

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

Melynn Nuite, RN BS CCRC

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: May 5, 2020
• Study Start: November 3, 2020
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)