Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial)
Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial)
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DOI：
10.1186/s12871-017-0339-x
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发表时间：
2017-03-21
影响因子：
2.2
通讯作者：
Eikermann, Matthias
中科院分区：
文献类型：
--
作者：
Anstey, Matthew H.;Wibrow, Bradley;Eikermann, Matthias
背景：入住重症监护室（ICU）的患者经常接受静脉（IV）血管加压药治疗。持续性低血压和依赖静脉血管加压药，否则复苏的患者导致延迟从ICU出院。米多君是一种口服α-1肾上腺素能激动剂，获批用于治疗症状性直立性低血压。这项试验的目的是评估是否口服米多君是一种有效的辅助标准治疗，以减少持续时间的IV血管加压药治疗，并允许早日出院ICU和hospital.Methods：MIDAS试验是一项国际，多中心，随机，双盲，安慰剂对照的临床试验正在美国和澳大利亚进行。我们的目标是120名患者。将考虑招募接受低剂量IV血管加压药治疗至少24小时后复苏且在其他方面稳定的入住ICU的成人患者。参与者将随机接受米多君（20毫克）或安慰剂，每天三次，除了标准的护理。主要结局是从开始米多君或安慰剂治疗到停用IV血管加压药的时间（小时）。次要结果包括从ICU入院到出院准备就绪的时间（小时），ICU住院时间（LOS）（天），医院LOS（天），ICU再入院率，以及与米多君administration.Discussion相关的不良事件率：米多君被美国食品和药物管理局（FDA）批准用于治疗症状性体位性低血压。2010年8月，FDA建议撤回对米多君的批准，因为缺乏验证该药物临床益处的研究。我们获得了新药研究（IND 113，330）批准，以研究其在需要IV血管加压药但准备从ICU出院的重症患者中的作用。在外科ICU患者队列中进行的一项初步观察性研究显示，开始米多君治疗后，血管加压药需求的下降率增加。我们假设米多君给药可以有效地停用静脉血管加压药，缩短ICU和医院的LOS。这项试验可能对降低医院护理成本和获得FDA批准米多君的新适应症具有重要意义。
Background: Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital.Methods: The MIDAS trial is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in the USA and Australia. We are targeting 120 patients. Adult patients admitted to the ICU who are resuscitated and otherwise stable on low dose IV vasopressors for at least 24 h will be considered for recruitment. Participants will be randomized to receive midodrine (20 mg) or placebo three times a day, in addition to standard care. The primary outcome is time (hours) from initiation of midodrine or placebo to discontinuation of IV vasopressors. Secondary outcomes include time (hours) from ICU admission to discharge readiness, ICU length of stay (LOS) (days), hospital LOS (days), rates of ICU readmission, and rates of adverse events related to midodrine administration.Discussion: Midodrine is approved by the Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension. In August 2010, FDA proposed to withdraw approval of midodrine because of lack of studies that verify the clinical benefit of the drug. We obtained Investigational New Drug (IND 113,330) approval to study its effects in critically ill patients who require IV vasopressors but are otherwise ready for discharge from the ICU. A pilot observational study in a cohort of surgical ICU patients showed that the rate of decline in vasopressor requirements increased after initiation of midodrine treatment. We hypothesize that midodrine administration is effective to wean IV vasopressors and shorten ICU and hospital LOS. This trial may have significant implications on lowering costs of hospital care and obtaining FDA approval for new indications for midodrine.