Merck & Co., Inc., Kenilworth, NJ, USA.
Merck & Co., Inc., Kenilworth, NJ, USA.
Br J Anaesth. 2018 Oct;121(4):749-757. doi: 10.1016/j.bja.2018.05.056. Epub 2018 Aug 23.
We evaluated the incidence of hypersensitivity or anaphylaxis after repeated single-dose sugammadex administration in non-anaesthetised adults.
In this multicentre, double-blind study (NCT02028065), healthy volunteer subjects were randomised (2:2:1 ratio) to one of three groups to receive three repeated intravenous injections of sugammadex 4 or 16 mg kg, or placebo, separated by a ∼5 week intervals. Targeted hypersensitivity assessments were performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were referred to a blinded independent Adjudication Committee. Anaphylaxis was determined per Sampson (Criterion 1). The primary endpoint was the proportion with confirmed hypersensitivity.
Of 375 evaluable subjects, 25 had confirmed hypersensitivity [sugammadex 4 mg kg: 10/151 (6.6%); sugammadex 16 mg kg: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs placebo were 5.3% (95% confidence interval: -0.9, 10.7) for sugammadex 4 mg kg and 8.1% (1.7, 14.2) for 16 mg kg. Incidence was similar across sugammadex doses and dosing occasions, including in subjects with reactions to previous doses. Three subjects (16 mg kg group) required antihistamines/corticosteroids and discontinued the study, per protocol; symptoms resolved and no subject required epinephrine. One subject with anaphylaxis after the first 16 mg kg dose recovered completely post-treatment. There were no clinically relevant anti-sugammadex antibody or tryptase findings.
Hypersensitivity in response to sugammadex administration can occur in healthy subjects without history of previous sugammadex exposure. Hypersensitivity incidence was similar across sugammadex doses and numerically higher than placebo, with no evidence of sensitisation with repeated administration. Hypersensitivity is unlikely to be mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell stimulation in healthy volunteers.
NCT02028065.
我们评估了非麻醉成年人重复单次给予氨甲环酸后过敏或过敏反应的发生率。
在这项多中心、双盲研究（NCT02028065）中，健康志愿者受试者按 2:2:1 的比例随机分为三组，分别接受 4 或 16mg/kg 三次重复静脉注射氨甲环酸，间隔约 5 周。在给药后 0.5、4 和 24 小时进行靶向过敏评估，并将过敏症状/体征提交给一个盲法独立裁决委员会。过敏反应根据 Sampson（标准 1）确定。主要终点是确证过敏的比例。
在 375 名可评估的受试者中，有 25 名确证过敏[4mg/kg 氨甲环酸组：151 例中有 10 例（6.6%）；16mg/kg 氨甲环酸组：148 例中有 14 例（9.5%）；安慰剂组：76 例中有 1 例（1.3%）]。与安慰剂相比，4mg/kg 氨甲环酸组和 16mg/kg 氨甲环酸组的发生率差异分别为 5.3%（95%置信区间：-0.9，10.7）和 8.1%（1.7，14.2）。在氨甲环酸剂量和给药次数方面，包括在对先前剂量有反应的受试者中，发生率相似。3 名受试者（16mg/kg 组）按方案需要抗组胺药/皮质类固醇治疗并退出研究；症状缓解，无受试者需要肾上腺素。1 名首次接受 16mg/kg 剂量后发生过敏反应的受试者经治疗后完全康复。没有发现与氨甲环酸相关的抗体或类胰蛋白酶的临床相关发现。
在没有先前接触过氨甲环酸史的健康受试者中，给予氨甲环酸后会发生过敏反应。在氨甲环酸剂量方面，过敏发生率相似，略高于安慰剂，且重复给药无致敏证据。在健康志愿者中，过敏反应不太可能通过氨甲环酸特异性免疫球蛋白 G 或 E 介导的肥大细胞刺激介导。
NCT02028065。
