为了解决美国阿片类药物的流行,临床上迫切需要为患有阿片类药物使用障碍(OUD)的人提供有效的OUD(MOUD)药物治疗。舌下丁丙诺啡/纳洛酮(SL-BUP/NLX)的制剂被认为是OUD的护理标准,包括在退伍军人医疗保健管理局(VHA)内。然而,对MOUD的保留不力会损害其有效性。长效可注射每月丁丙诺啡(INJ-BUP)(例如,Sublocade®)具有改善保留的潜力,因此可以减少阿片类药物的使用和过量。为OUD设计和进行研究带来了独特的挑战。在设计合作研究计划(CSP)2014,丁丙诺啡治疗退伍军人阿片类药物使用障碍(VA-BRAVE)时,这些考虑因素的策略和解决方案,一个随机的,20-site,在VHA内进行的比较INJ-BUP与SL-BUP/NLX的临床有效性试验可能为面临类似研究挑战的其他人提供有价值的指导.
这52周,平行组,开放标签,随机对照试验(RCT)评估了两种目前FDA批准的丁丙诺啡制剂的比较有效性:(1)每日SL-BUP/NLX与(2)每月(28天)INJ-BUP用于中度至重度OUD的退伍军人(n=952)。主要结果是(1)在MOUD中的保留和(2)阿片类药物禁欲。次要结果包括其他药物使用的衡量标准,精神症状,医疗结果,包括艾滋病毒的患病率,乙型肝炎和丙型肝炎以及社会结果(住房不稳定,刑事司法参与),服务利用率和成本效益。还包括对该人群进行比较有效性试验以及在COVID-19大流行期间的特殊考虑因素。
在现实世界的VHA环境中,与标准舌下制剂相比,对丁丙诺啡缓释制剂的评估对于解决阿片类药物流行至关重要。这种新的治疗方法在多大程度上促进了保留,减少阿片类药物的使用,迄今为止,尚未在任何长期试验中研究过预防OUD的严重后遗症。这项试验的积极结果可能导致MOUD的广泛采用,and,如果被证明是优越的INJ-BUP,整个VHA及其他地区的临床医生。这种治疗有可能减少退伍军人使用阿片类药物,提高医疗水平,心理,和社会结果,以合理的代价挽救生命。试验注册在Clinicaltrials.govNCT04375033注册。
To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness
trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges.
This 52-week, parallel group, open-label, randomized controlled
trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness
trial with this population and during COVID-19 pandemic were also included.
The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this
trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost.
Trial registration Registered at Clinicaltrials.gov NCT04375033.