Opioid Use Disorder
Conditions
Keywords
Buprenorphine, Veterans, Clinical Trial, Opioid Abstinence, Retention in Care, Pharmacotherapy
Brief summary
VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous formulation of buprenorphine at a target dose of 300 milligrams (mg) 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
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.
Interventions
DRUGSublingual 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.
DRUGInjectable 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.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 Medications for Opioid Use Disorder (MOUD) via clinical induction on SL-BUP/NLX * Meets DSM-5 criteria for moderate to severe opioid use disorder (OUD) based on the Mini-International Neuropsychiatric Interview * Referred to/seeking treatment for OUD and willing to accept "partial-agonist-based" therapy
Exclusion criteria
* 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 4 milligrams (mg) - 32mg SL-BUP/NLX in 45 days or less * Taking a form of prescribed maintenance Medications for Opioid Use Disorder (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 Sedative, Hypnotic, or Anxiolytic Use Disorder (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention in Treatment Change | 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. |
| Opioid Abstinence | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accidental Opioid Poisoning (overdose) | 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. |
| 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) | 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. |
| 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) | 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. |
| Other Addictive Substances | 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. |
| Opioid Craving | 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." |
| HIV Sexual and Injection Risk Behaviors | 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. |
| Patient Health Questionnaire (PHQ-9) | Assessed at baseline, weeks 12, 24, 36, and 52 | A measure of depressive symptoms (overall) and suicidality (item 9) |
| Post-traumatic stress disorder (PTSD) Checklist for DSM-5 | Assessed at baseline, weeks 12, 24, 36, and 52 | A measure of PTSD symptoms |
| Texas Christian University Criminal Justice Form | Assessed at baseline, weeks 12, 24, 36, and 52 | A measure of incarceration, arrests, criminal activity. |
| Dental Quality of Life Questionnaire | 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. |
Countries
United States
Contacts
CONTACTAvron Spiro, PhD MS
CONTACTMelynn Nuite, RN BS CCRC
STUDY_CHAIRIsmene L. Petrakis, MD
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
STUDY_CHAIRSandra Ann Springer, MD
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
Outcome results
None listed