A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder (VA-BRAVE)

February 27, 2024 updated by: VA Office of Research and Development

CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE)

VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous (in the belly area) 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 16-24 mg (standard of care). This is an open-label, randomized, controlled trial including 952 Veterans with opioid use disorder (OUD) recruited over 3 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 and 52-week active assessment period, 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 16-24 mg for 3 days (more than 3 days may be required if deemed clinically necessary; should not exceed 30 days). Once reaching the target dose, 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 15 new participants per study year per study site. There will be 20 participating VA Medical Center sites.

Study Type

Interventional

Enrollment (Estimated)

952

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Tuscaloosa, Alabama, United States, 35404-5015
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • Recruiting
        • Phoenix VA Health Care System, Phoenix, AZ
        • Contact:
    • California
      • Long Beach, California, United States, 90822
      • Palo Alto, California, United States, 94304-1207
      • San Francisco, California, United States, 94121-1563
    • Connecticut
      • West Haven, Connecticut, United States, 06516-2770
        • Recruiting
        • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
        • Contact:
        • Contact:
        • Study Chair:
          • Ismene L. Petrakis, MD
        • Study Chair:
          • Sandra Ann Springer, MD
      • West Haven, Connecticut, United States, 06516-2770
    • Florida
      • Bay Pines, Florida, United States, 33744-0000
      • Gainesville, Florida, United States, 32608-1135
        • Recruiting
        • North Florida/South Georgia Veterans Health System, Gainesville, FL
        • Contact:
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • Terminated
        • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417-2309
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Terminated
        • Louis Stokes VA Medical Center, Cleveland, OH
      • Dayton, Ohio, United States, 45428
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
      • Pittsburgh, Pennsylvania, United States, 15240
        • Terminated
        • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
    • Rhode Island
      • Providence, Rhode Island, United States, 02908-4734
    • Texas
      • Dallas, Texas, United States, 75216-7167
        • Recruiting
        • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
        • Contact:
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84148-0001
        • Recruiting
        • VA Salt Lake City Health Care System, Salt Lake City, UT
        • Contact:
        • Contact:
    • Vermont
      • White River Junction, Vermont, United States, 05001-3833
        • Recruiting
        • White River Junction VA Medical Center, White River Junction, VT
        • Contact:
        • Contact:
    • Virginia
      • Hampton, Virginia, United States, 23667
        • Recruiting
        • Hampton VA Medical Center, Hampton, VA
        • Contact:
        • Contact:
      • Salem, Virginia, United States, 24153-6404
    • Washington
      • Seattle, Washington, United States, 98108-1532
    • West Virginia
      • Huntington, West Virginia, United States, 25704-9300
        • Not yet recruiting
        • Huntington VA Medical Center, Huntington, WV
        • Contact:
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53295-0001
        • Recruiting
        • Clement J. Zablocki VA Medical Center, Milwaukee, WI
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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
  • Taking a form of prescribed maintenance MOUD (e.g., methadone, buprenorphine or XR-NTX) continuously >30 days prior to consent.
  • 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
  • Is determined unsuitable for study participation based on the clinical judgement of the LSI or Co-I given results of a CIWA-Ar, physical exam, and/or liver or kidney function tests and/or blood tests
  • Has any other medical, psychiatric, behavioral, or logistical condition which, in the judgement of the LSI or Co-I, makes it unlikely the participant 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sublingual Arm

The sublingual buprenorphine contains naloxone in a ratio of 4:1 and will be prescribed. Consistent with the SAMHSA TIP 40 guidelines 75, 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 16-24mg that is standard practice. While the target dose is 16-24mg, doses may go as low as 8mg as occasionally patients prefer lower doses. SL-BUP/NLX will be prescribed at the randomization visit (28-day supply), then every 4 weeks until week 48.
Drug: 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.
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 in the abdomen 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
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 in the abdomen at each 28-day visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Time Frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Accidental Opioid Poisoning (overdose)
Time Frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Self-reported non-fatal accidental opioid poisoning, hospital records, and CDC data on fatal accidental drug poisoning (by state) will be used to indicate fatal and non-fatal accidental opioid poisoning.
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
Time Frame: Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)
Assessment will indicate positive seroconversion for HIV, HBV, or HCV based on HIV-1 p24 antigen/antibody with reflex HIV RNA viral load, HBV sAB, sAG with reflex HBV viral load if HBV sAG positive only, and HCV AB with reflex HCV viral load. These tests are recommended as standard care for Veterans with OUD.
Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)
Healthcare and Service Utilization
Time Frame: Assess from baseline approximately every 4 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
An indicator of healthcare and service utilization will be obtained using the Service Utilization Review Form (SURF) that assesses utilization of VHA inpatient and outpatient care clinics, SUD clinics, detoxification programs, and pharmacies located within the VHA and local hospitals. Participants' use of other treatments will be documented on the SURF; non-VA health services will also be captured using the SURF.
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
Time Frame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Measured by Timeline Followback (self-report measure of substance use) and urine toxicology free of other addictive substances. 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)
Opioid Craving
Time Frame: Approximately every 4 weeks through 52 weeks (active phase)
Opioid craving will be measured on a 10-point Likert scale in response to the question "Please indicate how much you are craving opioids right now."
Approximately every 4 weeks through 52 weeks (active phase)
HIV Sexual and Injection Risk Behaviors
Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52
HIV sexual and injection risk behaviors will be assessed using NIDA's HIV Risk Behavior tool.
Assessed at baseline, weeks 12, 24, 36, and 52
Patient Health Questionnaire (PHQ-9)
Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52
A measure of depressive symptoms (overall) and suicidality (item 9)
Assessed at baseline, weeks 12, 24, 36, and 52
PTSD Checklist for DSM-5
Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52
A measure of PTSD symptoms
Assessed at baseline, weeks 12, 24, 36, and 52
Texas Christian University Criminal Justice Form
Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52
A measure of incarceration, arrests, criminal activity.
Assessed at baseline, weeks 12, 24, 36, and 52
Dental Quality of Life Questionnaire
Time Frame: Assessed at baseline, weeks 24 and 52
Self-report measure assessing oral/dental health and quality of life, salivary function, access to and use of dental healthcare.
Assessed at baseline, weeks 24 and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Study Chair: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 3, 2020

Primary Completion (Estimated)

November 3, 2024

Study Completion (Estimated)

November 4, 2025

Study Registration Dates

First Submitted

April 3, 2020

First Submitted That Met QC Criteria

May 4, 2020

First Posted (Actual)

May 5, 2020

Study Record Updates

Last Update Posted (Actual)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 27, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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