House Stacey L, Matsuda Kazuko, O'Brien Geoffrey, Makhay Malath, Iwaki Yuichi, Ferguson Ian, Lovato Luis M, Lewis Lawrence M
Division of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
MediciNova, Inc., San Diego, CA, USA.
Respir Med. 2015 Oct;109(10):1268-73. doi: 10.1016/j.rmed.2015.08.003. Epub 2015 Aug 14.
Many patients with acute exacerbation of asthma are non-responders to inhaled β-adrenergic agonists. The goal of this study was to evaluate the safety and efficacy of intravenous bedoradrine (MN-221), a highly selective β2-adrenergic agonist, as adjunct to standard therapy in the management of patients with acute exacerbation of asthma who did not respond to standard therapy.
Patients (N = 167) received standard therapy and were randomized to either bedoradrine (1200 μg) or placebo. Safety and efficacy parameters were monitored hourly for 3 h, followed by a 24-h follow-up visit and an 8-day follow-up phone call. Change in %FEV1 from baseline to Hour 3 was the primary outcome. Secondary outcome measures included change in %FEV1 at 1 and 2 h, change in dyspnea score at 1, 2, and 3 h, treatment failure rate, defined as a combination of hospitalization on the index visit or return to the emergency department within 1 week, and safety monitoring.
There was no significant difference in %FEV1 at 3 h between the 2 groups. The dyspnea scores were significantly improved for patients treated with bedoradrine compared to placebo (AUC0-2 hP < 0.005, AUC0-3 hP < 0.05). The safety profile for those treated with bedoradrine was consistent with the known mechanism of action of β-adrenergic agonists, and included both cardiovascular and metabolic effects.
Intravenous bedoradrine, in addition to standard therapy, did not significantly increase %FEV1 at 3 h, but it was associated with significantly improved dyspnea scores.
Clinicaltrials.gov; study name: MN-221-CL-007, registration number: NCT00838591; www.clinical trials.gov.
许多哮喘急性加重患者对吸入性β-肾上腺素能激动剂无反应。本研究的目的是评估静脉注射贝多瑞林（MN-221），一种高选择性β2-肾上腺素能激动剂，作为标准治疗的辅助手段，用于治疗对标准治疗无反应的哮喘急性加重患者的安全性和有效性。
167例患者接受标准治疗，并随机分为贝多瑞林组（1200μg）或安慰剂组。每小时监测安全性和有效性参数，持续3小时，随后进行24小时随访和8天的随访电话。从基线到第3小时的FEV1%变化是主要结局。次要结局指标包括第1小时和第2小时的FEV1%变化、第1、2和3小时的呼吸困难评分变化、治疗失败率（定义为首次就诊时住院或1周内返回急诊科的综合情况）以及安全性监测。
两组在第3小时的FEV1%无显著差异。与安慰剂相比，接受贝多瑞林治疗的患者呼吸困难评分显著改善（AUC0 - 2hP < 0.005，AUC0 - 3hP < 0.05）。接受贝多瑞林治疗患者的安全性概况与β-肾上腺素能激动剂已知的作用机制一致，包括心血管和代谢效应。
除标准治疗外，静脉注射贝多瑞林在第3小时并未显著增加FEV1%，但与呼吸困难评分显著改善相关。
Clinicaltrials.gov；研究名称：MN - 221 - CL - 007，注册号：NCT00838591；网址：www.clinicaltrials.gov 。
