Bernstein Jonathan A, Moellman Joseph J, Collins Sean P, Hart Kimberly W, Lindsell Chris J
Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Internal Medicine, Division of Immunology/Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Ann Allergy Asthma Immunol. 2015 Mar;114(3):245-9. doi: 10.1016/j.anai.2014.12.007. Epub 2015 Jan 16.
Angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-AE) is mediated by bradykinin. There remains an unmet treatment need because these patients, when presenting to the emergency department (ED), do not respond to conventional therapies, such as antihistamines and corticosteroids.
To estimate the treatment effect of ecallantide, a recombinant plasma kallikrein inhibitor, in ED patients with ACEI-AE in whom conventional therapy fails.
This was a triple-blind (patient, physician, and statistician), randomized, controlled, phase 2 study to estimate the magnitude of safety and efficacy signals for designing a definitive phase 3 trial comparing conventional therapy with ecallantide to conventional therapy with placebo. Patients were enrolled from April 1, 2010, through January 31, 2013. The primary efficacy study end point was achieving discharge criteria from the ED within 4 hours after initiating study-related treatment.
Discharge criteria from the ED was met in 4 hours or less for 8 (31%) of 26 patients receiving ecallantide vs 5 of (21%) 24 patients receiving placebo (difference in proportions, 10%; 95% confidence interval, -14% to 34%). Ecallantide was well tolerated in both groups.
The results from this preliminary study reveal that ecallantide is safe to use and may increase the proportion of patients who meet early discharge criteria by approximately10%. A larger phase 3 study is necessary to confirm the efficacy and evaluate the cost-effectiveness of ecallantide use for ACEI-AE in the ED setting.
clinicaltrials.gov Identifier: NCT01036659.
血管紧张素转换酶抑制剂诱发的血管性水肿（ACEI-AE）由缓激肽介导。由于这些患者在急诊科就诊时对常规疗法（如抗组胺药和皮质类固醇）无反应，因此仍存在未满足的治疗需求。
评估重组血浆激肽释放酶抑制剂依卡凝血素对常规治疗无效的ACEI-AE急诊患者的治疗效果。
这是一项三盲（患者、医生和统计学家）、随机、对照的2期研究，旨在评估安全性和疗效信号的强度，以便设计一项确定性的3期试验，将依卡凝血素联合常规治疗与安慰剂联合常规治疗进行比较。患者于2010年4月1日至2013年1月31日入组。主要疗效研究终点是在开始与研究相关的治疗后4小时内达到急诊科出院标准。
26例接受依卡凝血素治疗的患者中有8例（31%）在4小时或更短时间内达到急诊科出院标准，而24例接受安慰剂治疗的患者中有5例（21%）达到该标准（比例差异为10%；95%置信区间为-14%至34%）。两组对依卡凝血素的耐受性均良好。
这项初步研究的结果表明，依卡凝血素使用安全，可能会使符合早期出院标准的患者比例增加约10%。有必要进行一项更大规模的3期研究，以确认依卡凝血素在急诊科治疗ACEI-AE的疗效并评估其成本效益。
clinicaltrials.gov标识符：NCT01036659。
