A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema
A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema
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DOI：
10.1056/nejmoa1312524
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发表时间：
2015-01-29
影响因子：
158.5
通讯作者：
Hoffmann, Thomas K.
中科院分区：
文献类型：
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作者：
Bas, Murat;Greve, Jens;Hoffmann, Thomas K.
血管紧张素转换酶（ACE）抑制剂治疗引起的血管性水肿占急诊室血管性水肿病例的三分之一;它通常表现在上呼吸道和头颈部。没有批准的治疗这种潜在的危及生命的condition. METHODS在这个多中心，双盲，双模拟，随机2期研究中，我们分配患者谁有ACE抑制剂诱导的上呼吸消化道血管性水肿治疗30毫克皮下艾替班特，选择性缓激肽B2受体拮抗剂，或目前的标签外标准治疗，包括静脉内泼尼松龙（500 mg）加氯马斯汀（2 mg）。主要疗效终点是水肿完全消退的中位时间。符合方案人群中所有27例患者水肿完全消退。艾替班特组至完全缓解的中位时间为8.0小时（四分位距，3.0 - 16.0），而标准治疗组为27.1小时（四分位距，20.3 - 48.0）（P = 0.002）。3例接受标准治疗的患者需要使用艾替班特和泼尼松龙进行补救干预; 1例患者需要气管切开术。治疗后4小时内，艾替班特组水肿完全消退的患者显著多于标准治疗组（13例中5例vs. 14例中0例，P = 0.02）。与标准治疗相比，艾替班特治疗组至症状缓解的中位时间（根据复合评估者评估的症状评分）显著缩短（2.0小时vs. 11.7小时，P = 0.03）。当患者评估的症状评分used.CONCLUSIONSAmong患者ACE抑制剂诱导的血管性水肿，水肿完全解决的时间是显着较短的艾替班特比联合治疗与糖皮质激素和抗组胺药。
BACKGROUNDAngioedema induced by treatment with angiotensin-converting-enzyme (ACE) inhibitors accounts for one third of angioedema cases in the emergency room; it is usually manifested in the upper airway and the head and neck region. There is no approved treatment for this potentially life-threatening condition.METHODSIn this multicenter, double-blind, double-dummy, randomized phase 2 study, we assigned patients who had ACE-inhibitor-induced angioedema of the upper aerodigestive tract to treatment with 30 mg of subcutaneous icatibant, a selective bradykinin B2 receptor antagonist, or to the current off-label standard therapy consisting of intravenous prednisolone (500 mg) plus clemastine (2 mg). The primary efficacy end point was the median time to complete resolution of edema.RESULTSAll 27 patients in the per-protocol population had complete resolution of edema. The median time to complete resolution was 8.0 hours (interquartile range, 3.0 to 16.0) with icatibant as compared with 27.1 hours (interquartile range, 20.3 to 48.0) with standard therapy (P = 0.002). Three patients receiving standard therapy required rescue intervention with icatibant and prednisolone; 1 patient required tracheotomy. Significantly more patients in the icatibant group than in the standard-therapy group had complete resolution of edema within 4 hours after treatment (5 of 13 vs. 0 of 14, P = 0.02). The median time to the onset of symptom relief (according to a composite investigator-assessed symptom score) was significantly shorter with icatibant than with standard therapy (2.0 hours vs. 11.7 hours, P = 0.03). The results were similar when patient-assessed symptom scores were used.CONCLUSIONSAmong patients with ACE-inhibitor-induced angioedema, the time to complete resolution of edema was significantly shorter with icatibant than with combination therapy with a glucocorticoid and an antihistamine.