Effect of Intranasal vs Intramuscular Naloxone on Opioid Overdose A Randomized Clinical Trial
Effect of Intranasal vs Intramuscular Naloxone on Opioid Overdose A Randomized Clinical Trial
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DOI：
10.1001/jamanetworkopen.2019.14977
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发表时间：
2019-11-01
影响因子：
13.8
通讯作者：
Kerr, Debra
中科院分区：
文献类型：
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作者：
Dietze, Paul;Jauncey, Marianne;Kerr, Debra
重要性 先前的非盲临床试验表明，盐酸纳洛酮的鼻内途径在逆转阿片类药物过量方面不如广泛使用的肌肉注射途径。 目的 测试鼻内给药剂量的纳洛酮在逆转阿片类药物过量方面是否与相同剂量的肌肉注射纳洛酮一样有效。 设计、设置和参与者双模拟随机临床试验在澳大利亚悉尼联合医疗监督注射中心进行。该中心招募的客户于2012年2月1日至2017年1月3日期间参与。符合资格的客户年龄在18岁或以上，有注射吸毒史（n = 197）。对接受鼻内和肌内治疗模式（主动或安慰剂）的所有参与者进行意向治疗分析。 干预措施 患者被随机接受 2 种治疗中的 1 种：(1) 鼻内给予盐酸纳洛酮 800 μg/1mL，肌内给予安慰剂 1mL 或 (2) 肌内给予盐酸纳洛酮 800 μg/1mL，然后鼻内给予安慰剂1mL。主要结果和测量主要结果测量是在初始治疗后10分钟需要肌内注射盐酸纳洛酮(800μg)的救援剂量。次要结局指标包括达到每分钟呼吸次数大于或等于 10 次的充足呼吸时间以及达到大于或等于 13 分的格拉斯哥昏迷量表评分的时间。 结果 共有 197 名患者（173 [87.8%] 男性；平均 [SD] 年龄，34.0 [7.82] 岁）完成了试验，其中 93 名 (47.2%) 被随机分配至肌肉注射纳洛酮剂量，104 名患者被随机分配至肌肉注射纳洛酮剂量。 (52.8%) 鼻内纳洛酮剂量。与随机接受鼻内纳洛酮给药的患者相比，随机接受肌内纳洛酮给药的患者不太可能需要救援剂量的纳洛酮（8 [8.6%] vs 24 [23.1%]；比值比，0.35；95% CI，0.15-0.66；P = 0.002）。呼吸频率时间至少为 10 时，风险增加 65%（风险比，1.65；95% CI，1.21-2.25；P = .002）；格拉斯哥昏迷量表评分至少为 10 时，风险增加 81%（风险比，1.81；95% CI，1.28-2.56；P = .001）与接受肌肉注射纳洛酮的组相比，接受鼻内纳洛酮的组观察到 13 例。两组均未报告重大不良事件。 结论和相关性 该试验表明，在监督注射设施中鼻内施用纳洛酮可以逆转阿片类药物过量，但不如肌内施用纳洛酮有效，这一结果在很大程度上重复了之前的非盲临床试验的结果。这些结果表明，确定鼻内纳洛酮的最佳剂量和浓度以应对现实条件下阿片类药物过量是国际优先事项。
IMPORTANCE Previous unblinded clinical trials suggested that the intranasal route of naloxone hydrochloridewas inferior to the widely used intramuscular route for the reversal of opioid overdose.OBJECTIVE To test whether a dose of naloxone administered intranasally is as effective as the same dose of intramuscularly administered naloxone in reversing opioid overdose.DESIGN, SETTING, AND PARTICIPANTS A double-blind, double-dummy randomized clinical trial was conducted at the Uniting Medically Supervised Injecting Centre in Sydney, Australia. Clients of the center were recruited to participate from February 1, 2012, to January 3, 2017. Eligible clients were aged 18 years or older with a history of injecting drug use (n = 197). Intention-to-treat analysis was performed for all participants who received both intranasal and intramuscular modes of treatment (active or placebo).INTERVENTIONS Clients were randomized to receive 1 of 2 treatments: (1) intranasal administration of naloxone hydrochloride 800 mu g per 1mL and intramuscular administration of placebo 1mL or (2) intramuscular administration of naloxone hydrochloride 800 mu g per 1 mL and intranasal administration of placebo 1mL.MAIN OUTCOMES AND MEASURES The primary outcome measure was the need for a rescue dose of intramuscular naloxone hydrochloride (800 mu g) 10 minutes after the initial treatment. Secondary outcome measures included time to adequate respiratory rate greater than or equal to 10 breaths per minute and time to Glasgow Coma Scale score greater than or equal to 13.RESULTS A total of 197 clients (173 [87.8%] male; mean [SD] age, 34.0 [7.82] years) completed the trial, of whom 93 (47.2%) were randomized to intramuscular naloxone dose and 104 (52.8%) to intranasal naloxone dose. Clients randomized to intramuscular naloxone administration were less likely to require a rescue dose of naloxone compared with clients randomized to intranasal naloxone administration (8 [8.6%] vs 24 [23.1%]; odds ratio, 0.35; 95% CI, 0.15-0.66; P = .002). A 65% increase in hazard (hazard ratio, 1.65; 95% CI, 1.21-2.25; P = .002) for time to respiratory rate of at least 10 and an 81% increase in hazard (hazard ratio, 1.81; 95% CI, 1.28-2.56; P = .001) for time to Glasgow Coma Scale score of at least 13 were observed for the group receiving intranasal naloxone compared with the group receiving intramuscular naloxone. No major adverse events were reported for either group.CONCLUSIONS AND RELEVANCE This trial showed that intranasally administered naloxone in a supervised injecting facility can reverse opioid overdose but not as efficiently as intramuscularly administered naloxone can, findings that largely replicate those of previous unblinded clinical trials. These results suggest that determining the optimal dose and concentration of intranasal naloxone to respond to opioid overdose in real-world conditions is an international priority.