Department of Psychiatry, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Addict Sci Clin Pract. 2022 Jan 31;17(1):6. doi: 10.1186/s13722-022-00286-6.
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.
为了解决美国阿片类药物泛滥的问题，迫切需要为患有阿片类药物使用障碍（OUD）的患者提供有效的药物治疗（MOUD）。舌下含服丁丙诺啡/纳洛酮（SL-BUP/NLX）制剂被认为是 OUD 的标准治疗方法，包括在退伍军人医疗保健管理局（VHA）内。然而，MOUD 的保留率低会降低其效果。长效每月注射丁丙诺啡（INJ-BUP）（例如，Sublocade®）有可能提高保留率，从而减少阿片类药物的使用和过量。OUD 的研究设计和实施带来了独特的挑战。在设计合作研究计划（CSP）2014 中，为一些考虑因素制定的策略和解决方案，即退伍军人中丁丙诺啡治疗阿片类药物使用障碍（VA-BRAVE），一项随机、20 个地点、临床有效性试验，比较 INJ-BUP 与 SL-BUP/NLX 在 VHA 内进行，可能为其他面临类似调查挑战的人提供有价值的指导。
这项为期 52 周的、平行组、开放标签、随机对照试验（RCT）评估了两种当前 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 用于患有中度至重度 OUD 的退伍军人（n=952）。主要结局是（1）MOUD 的保留率和（2）阿片类药物戒断。次要结局包括其他药物使用、精神病症状、医疗结果（包括 HIV、乙型肝炎和丙型肝炎的流行率）以及社会结果（住房不稳定、刑事司法参与）、服务利用和成本效益的衡量标准。还包括在具有这种人群的现实环境中以及在 COVID-19 大流行期间进行比较有效性试验的特殊考虑因素。
在 VHA 环境中，在现实世界中比较丁丙诺啡的缓释制剂与标准舌下制剂的评估对于解决阿片类药物泛滥问题至关重要。到目前为止，还没有任何长期试验研究这种新治疗方法在提高保留率、减少阿片类药物使用和预防 OUD 严重后果方面的效果。如果本试验结果为阳性，可能会导致 MOUD 在 VHA 内外的广泛采用，如果证明新型 INJ-BUP 更优，则可能会在 VHA 内外的临床医生中广泛采用。这种治疗方法有可能减少退伍军人的阿片类药物使用，改善医疗、心理和社会结果，并以合理的成本挽救生命。试验注册在 Clinicaltrials.gov 上注册为 NCT04375033。
