Merck & Co., Inc., Kenilworth, NJ, USA.
Centre for Human Drug Research and Leiden University, Leiden, The Netherlands.
Br J Anaesth. 2018 Oct;121(4):758-767. doi: 10.1016/j.bja.2018.05.057. Epub 2018 Jul 13.
We investigated potential for hypersensitivity reactions after repeated sugammadex administration and explored the mechanism of hypersensitivity.
In this double-blind, placebo-controlled study (NCT00988065), 448 healthy volunteers were randomised to one of three arms to receive three repeat i.v. administrations of either sugammadex 4 mg kg, 16 mg kg, or placebo. Primary endpoint was percentage of subjects with hypersensitivity (assessed by an independent adjudication committee). Secondary endpoint of anaphylaxis was classified per Sampson and Brighton criteria. Exploratory endpoints included skin testing, serum tryptase, anti-sugammadex antibodies [immunoglobulin (Ig) E/IgG], and other immunologic parameters.
Hypersensitivity was adjudicated for 1/148 (0.7%), 7/150 (4.7%), and 0/150 (0.0%) subjects after sugammadex 4 mg kg, 16 mg kg, and placebo, respectively. After sugammadex 16 mg kg, one subject met Sampson criterion 1 and Brighton level 1 (highest certainty) anaphylaxis criteria; two met Brighton level 2 criteria. After database lock it was determined that certain protocol deviations could have introduced bias in the reporting of hypersensitivity signs/symptoms in a subject subset. Objective laboratory investigations indicated that potential underlying hypersensitivity mechanisms were unlikely to have been activated; the results suggest that most of the observed hypersensitivity reactions were unlikely IgE/IgG-mediated.
Dose-dependent hypersensitivity or anaphylaxis reactions to sugammadex were observed when administered without prior neuromuscular blocking agent. Laboratory investigations do not suggest prevalent allergen-specific IgE/IgG-mediated immunologic hypersensitivity. Because it could not be fully excluded that estimates of hypersensitivity/anaphylaxis incidence were unbiased, an additional study was conducted to characterise the potential for hypersensitivity reactions and is described in a companion report.
http://www.clinicaltrials.gov NCT00988065; Protocol number P06042.
我们研究了重复给予琥珀酸舒更葡糖钠后发生超敏反应的可能性，并探讨了超敏反应的机制。
在这项双盲、安慰剂对照研究（NCT00988065）中，448 名健康志愿者随机分为三组，分别接受静脉重复给予琥珀酸舒更葡糖钠 4mg/kg、16mg/kg 或安慰剂。主要终点是超敏反应（由独立裁决委员会评估）的发生率。过敏反应的次要终点按照 Sampson 和 Brighton 标准分类。探索性终点包括皮肤试验、血清类胰蛋白酶、抗琥珀酸舒更葡糖钠抗体[免疫球蛋白（Ig）E/IgG]和其他免疫参数。
在琥珀酸舒更葡糖钠 4mg/kg、16mg/kg 和安慰剂组中，分别有 1/148（0.7%）、7/150（4.7%）和 0/150（0.0%）名受试者被判定为超敏反应。在琥珀酸舒更葡糖钠 16mg/kg 组中，1 名受试者符合 Sampson 标准 1 和 Brighton 水平 1（最高确定性）过敏反应标准；2 名受试者符合 Brighton 水平 2 标准。在数据库锁定后确定，某些方案偏差可能导致在一组受试者中报告超敏反应体征/症状时出现偏倚。客观实验室研究表明，潜在的超敏反应机制不太可能被激活；结果表明，大多数观察到的超敏反应不太可能是 IgE/IgG 介导的。
在没有预先使用神经肌肉阻滞剂的情况下给予琥珀酸舒更葡糖钠时，观察到剂量依赖性的超敏反应或过敏反应。实验室研究不表明普遍存在过敏原特异性 IgE/IgG 介导的免疫超敏反应。由于不能完全排除超敏反应/过敏反应发生率的估计是无偏的，因此进行了一项额外的研究来描述超敏反应的可能性，并在一篇配套报告中进行了描述。
http://www.clinicaltrials.gov NCT00988065；方案编号 P06042。
