Clinical trial NCT04375033: A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder
Official title: CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Opioid Use Disorder
Keywords: Buprenorphine
Veterans
Clinical Trial
Opioid Abstinence
Retention in Care
Pharmacotherapy
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2020-05-05
Enrollment: 952
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

Brief summary: 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 16-32 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: 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 16-32 mg for 3 days (more than 3 days may be required if deemed clinically necessary; 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.

Eligibility criteria: 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
* Failure to reach maintenance dose of 8mg - 32mg SL-BUP/NLX in 45 days or less (must have taken 3 consecutive days of maintenance dose immediately before randomization).
* 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.

Primary outcomes:
measure: Retention in Treatment Change
timeFrame: Approximately every 4 weeks until the first period of missed prescription medication coverage lasting at least 4 weeks through week 52
measure: Opioid Abstinence
timeFrame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
Secondary outcomes:
measure: Accidental Opioid Poisoning (overdose)
timeFrame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
measure: Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) seroconversion
timeFrame: Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)
measure: Healthcare and Service Utilization
timeFrame: Assess from baseline approximately every 4 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
measure: Other Addictive Substances
timeFrame: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)
measure: Opioid Craving
timeFrame: Approximately every 4 weeks through 52 weeks (active phase)
measure: HIV Sexual and Injection Risk Behaviors
timeFrame: Assessed at baseline, weeks 12, 24, 36, and 52
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: Assessed at baseline, weeks 12, 24, 36, and 52
measure: PTSD Checklist for DSM-5
timeFrame: Assessed at baseline, weeks 12, 24, 36, and 52
measure: Texas Christian University Criminal Justice Form
timeFrame: Assessed at baseline, weeks 12, 24, 36, and 52
measure: Dental Quality of Life Questionnaire
timeFrame: Assessed at baseline, weeks 24 and 52
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Tuscaloosa VA Medical Center, Tuscaloosa, AL
state: Alabama
city: Phoenix
country: United States
facility: Phoenix VA Health Care System, Phoenix, AZ
state: Arizona
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System, Palo Alto, CA
state: California
city: San Francisco
country: United States
facility: San Francisco VA Medical Center, San Francisco, CA
state: California
city: West Haven
country: United States
facility: CERC (VISN1, West Haven, CT)
state: Connecticut
city: West Haven
country: United States
facility: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
state: Connecticut
city: Wilmington
country: United States
facility: Wilmington VA Medical Center, Wilmington, DE
state: Delaware
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System, Pay Pines, FL
state: Florida
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System, Gainesville, FL
state: Florida
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Cleveland
country: United States
facility: Louis Stokes VA Medical Center, Cleveland, OH
state: Ohio
city: Dayton
country: United States
facility: Dayton VA Medical Center, Dayton, OH
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia MultiService Center, Philadelphia, PA
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
state: Pennsylvania
city: Providence
country: United States
facility: Providence VA Medical Center, Providence, RI
state: Rhode Island
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
city: White River Junction
country: United States
facility: White River Junction VA Medical Center, White River Junction, VT
state: Vermont
city: Hampton
country: United States
facility: Hampton VA Medical Center, Hampton, VA
state: Virginia
city: Salem
country: United States
facility: Salem VA Medical Center, Salem, VA
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
city: Huntington
country: United States
facility: Huntington VA Medical Center, Huntington, WV
state: West Virginia
city: Milwaukee
country: United States
facility: Clement J. Zablocki VA Medical Center, Milwaukee, WI
state: Wisconsin
Study officials:
affiliation: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
name: Ismene L. Petrakis, MD
role: STUDY_CHAIR
affiliation: VA Connecticut Healthcare System West Haven Campus, West Haven, CT
name: Sandra Ann Springer, MD
role: STUDY_CHAIR
References:
citation: 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.