A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder (VA-BRAVE)
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| ClinicalTrials.gov Identifier: NCT04375033 |
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Recruitment Status :
Recruiting
First Posted : May 5, 2020
Last Update Posted : November 27, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Opioid Use Disorder | Drug: Sublingual buprenorphine with naloxone Drug: Injectable subcutaneous buprenorphine | Phase 4 |
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 (Clinical Trial) |
| Estimated Enrollment : | 952 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| 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). |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | CSP #2014 - Comparative Effectiveness of Two Formulations of Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE) |
| Actual Study Start Date : | November 3, 2020 |
| Estimated Primary Completion Date : | November 3, 2024 |
| Estimated Study Completion Date : | November 4, 2025 |
| Arm | Intervention/treatment |
|---|---|
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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. |
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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.
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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. |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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."
- 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.
- 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)
- PTSD Checklist for DSM-5 [ Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52 ]A measure of PTSD symptoms
- Texas Christian University Criminal Justice Form [ Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52 ]A measure of incarceration, arrests, criminal activity.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04375033
| Contact: Avron Spiro, PhD MS | (857) 364-2888 | avron.spiro@va.gov | |
| Contact: Melynn Nuite, RN BS CCRC | (617) 232-9500 | Melynn.Nuite@va.gov |
Show 24 study locations
| 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 |
| Responsible Party: | VA Office of Research and Development |
| ClinicalTrials.gov Identifier: | NCT04375033 |
| Other Study ID Numbers: |
2014 |
| First Posted: | May 5, 2020 Key Record Dates |
| Last Update Posted: | November 27, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| 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 |
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Buprenorphine Veterans Clinical Trial Abstinence |
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Opioid-Related Disorders Substance-Related Disorders Narcotic-Related Disorders Chemically-Induced Disorders Mental Disorders Buprenorphine Naloxone Analgesics, Opioid |
Narcotics Central Nervous System Depressants Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Narcotic Antagonists |