A Study Comparing Oral Buprenorphine and Injectable Buprenorphine for the Treatment of Opioid Use Disorder

Официальное название

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

Обзор

VA-BRAVE will determine whether a 28-day long-acting injectable sub-cutaneous 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 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.

Подробное описание

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.

Вмешательства

• Препарат 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 through Week 48.
• Препарат 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 at each 28-day visit through Week 48.

Первичные конечные точки

• Retention in Treatment Change [Срок оценки: Approximately every 4 weeks until the first period of missed prescription medication coverage lasting at least 4 weeks through week 52]
• Opioid Abstinence [Срок оценки: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)]

Вторичные конечные точки (10)

• Accidental Opioid Poisoning (overdose) [Срок оценки: 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 [Срок оценки: Assessed at baseline, week 24, week 52 (active phase) and via EMR review for up to 10 years (passive phase)]
• Healthcare and Service Utilization [Срок оценки: 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 [Срок оценки: Approximately every 2 weeks through 52 weeks (active phase) and via EMR review for up to 10 years (passive phase)]
• Opioid Craving [Срок оценки: Approximately every 4 weeks through 52 weeks (active phase)]
• HIV Sexual and Injection Risk Behaviors [Срок оценки: Assessed at baseline, weeks 12, 24, 36, and 52]
• Patient Health Questionnaire (PHQ-9) [Срок оценки: Assessed at baseline, weeks 12, 24, 36, and 52]
• PTSD Checklist for DSM-5 [Срок оценки: Assessed at baseline, weeks 12, 24, 36, and 52]
• Texas Christian University Criminal Justice Form [Срок оценки: Assessed at baseline, weeks 12, 24, 36, and 52]
• Dental Quality of Life Questionnaire [Срок оценки: Assessed at baseline, weeks 24 and 52]

Критерии участия

Критерии включения

• 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 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

Критерии исключения

• 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 4mg - 32mg SL-BUP/NLX in 45 days or less.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 25 центров

• Tuscaloosa VA Medical Center, Tuscaloosa, AL — Tuscaloosa
• Phoenix VA Health Care System, Phoenix, AZ — Phoenix
• VA Long Beach Healthcare System, Long Beach, CA — Long Beach
• VA Palo Alto Health Care System, Palo Alto, CA — Palo Alto
• San Francisco VA Medical Center, San Francisco, CA — San Francisco
• CERC (VISN1, West Haven, CT) — West Haven
• VA Connecticut Healthcare System West Haven Campus, West Haven, CT — West Haven
• Wilmington VA Medical Center, Wilmington, DE — Wilmington
• … и ещё 17 центров

Публикации

• 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: PMID 35101115

Идентификаторы

NCT: NCT04375033 · 2014

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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