Strassen Ulrich, Bas Murat, Wirth Magdalena, Wirth Markus, Gröger Moritz, Stelter Klaus, Volkenstein Stefan, Kehl Victoria, Kojda Georg, Hoffmann Thomas K, Hahn Janina, Trainotti Susanne, Greve Jens
Department of Otorhinolaryngology, Klinikum rechts der Isar, Technische Universität München, Germany.
Department of Otorhinolaryngology, Klinikum rechts der Isar, Technische Universität München, Germany.
Am J Emerg Med. 2023 Feb;64:121-128. doi: 10.1016/j.ajem.2022.12.001. Epub 2022 Dec 5.
ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema.
We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR).
30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication.
In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.
血管紧张素转换酶抑制剂（ACEi）诱发的血管性水肿主要影响上呼吸道消化道。由于ACEi诱发的血管性水肿由缓激肽介导，因此对抗组胺药和糖皮质激素的治疗反应仍不尽人意。在缓激肽介导的遗传性血管性水肿中，C1酯酶抑制剂（C1INH）多年来一直是一种有效且获批的治疗方法。我们的目的是评估C1INH对ACEi诱发的血管性水肿的治疗效果。
我们在2013年12月至2018年9月期间进行了一项双盲、平行组、多中心随机安慰剂对照试验。符合条件的是患有ACEi诱发的血管性水肿且伴有气道阻塞的成年人。除了标准治疗（静脉注射500mg泼尼松龙和2.68mg氯马斯汀）外，参与者被1:1随机分配接受单剂量静脉注射C1INH（20IU/kg）或安慰剂（0.9%氯化钠）。在基线时以及直至48小时、出院时和出院后1周评估综合症状评分。医生评估水肿完全消退时间（TCER）和缓解开始时间（TOR）。
30名患者（16名接受C1INH，14名接受安慰剂）被随机分组并给药。25名（9名接受C1INH，12名接受安慰剂）完成了研究。C1INH组的TCER为29.63小时±15.56小时，安慰剂组为17.29小时±10.40小时（p = 0.0457）。C1INH组和安慰剂组的TOR分别为4.13小时±3.38小时和2.86小时±1.29小时（p = 0.4443）。没有与研究用药相关的不良事件。
在基线应用类固醇和抗组胺药的情况下，与安慰剂相比，C1INH在治疗ACEi诱发的血管性水肿方面，在症状完全消退时间上较差。欧盟临床试验编号：2012-001670-28。
