A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder (VA-BRAVE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04375033|
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : June 9, 2021
|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 :||900 participants|
|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)|
|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, 2023|
|Estimated Study Completion Date :||November 4, 2024|
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.
- 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.
- Quality of Life [ Time Frame: Assessed at baseline, weeks 12, 24, 36, and 52 ]Measure via the Veterans Rand-12, based on the 12-item Short Form Survey (SF12), a widely used measure of health-related quality of life. The VR-12 can be summarized resulting in a scale from 0 to 100, with higher scores indicating better quality of life.
- 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.
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: Cynthia R Davis, PhD||(617) 483-5465||Cynthia.Davis8@va.gov|
|Contact: Melynn Nuite, RN BS CCRC||(617) 232-9500||Melynn.Nuite@va.gov|
|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|