Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial
Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial
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DOI：
10.1016/j.drugalcdep.2018.02.023
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发表时间：
2018-06-01
影响因子：
4.2
通讯作者：
Sullivan, Maria A.
中科院分区：
文献类型：
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作者：
Bisaga, Adam;Mannelli, Paolo;Sullivan, Maria A.
背景：可注射的缓释纳曲酮（XR-NTX）被批准用于预防阿片类药物依赖复发，需要初始戒断。这项多中心门诊临床试验检测了低剂量口服纳曲酮（NTX）联合丁丙诺啡（BUP）短期逐渐减少和长期辅助药物对XR-NTX解毒和诱导的有效性和安全性。方法：患者（N = 378）随机分组，按主要短效阿片类药物分层，分为三种方案：NTX + BUP；NTX +安慰剂BUP (PBO-B)；安慰剂NTX (PBO-N) + PBO-B。患者在门诊接受7天的NTX或安慰剂递增治疗，同时接受3天BUP或安慰剂减量治疗，以及辅助药物治疗。每天提供心理教育咨询。第8天，通过纳洛酮挑战的患者接受XR-NTX治疗。结果：两组间向XR-NTX过渡的比率具有可比性：NTX/BUP（46.0%）、NTX/PBO-B（40.5%）、PBO-N/PBO-B（46.0%）。因此，该研究未达到其主要终点。32.5%的患者报告的不良事件严重程度为轻至中度，与阿片类药物戒断一致。第一次、第二次和第三次注射XR-NTX的患者分别为44.4%、29.9%和22.5%。与PBO-N/PBO-B组相比，NTX/BUP组在过渡期间表现出更高的阿片类药物戒断，xr -NTX后主观阿片类药物戒断评分较低。结论：单独使用NTX或NTX + BUP的7天解毒方案对XR-NTX的诱导率与安慰剂相似。对于那些诱导到XR-NTX的患者，在诱导前的阿片类戒断症状管理是在一个结构化的门诊环境中实现的，使用三组共同的耐受性良好的固定剂量辅助用药方案。
Background: Injectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX.Methods: Patients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX.Results: Rates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores.Conclusions: A 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.