Short-term application of tocilizumab during myocardial infarction (STAT-MI)
Short-term application of tocilizumab during myocardial infarction (STAT-MI)
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DOI：
10.1007/s00296-017-3842-y
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Smith, Christopher
中科院分区：
文献类型：
--
作者：
Carroll, Matthew B.;Haller, Charles;Smith, Christopher
急性心肌梗死（MI）发生时，血液供应低于临界水平和正常的细胞维持机制失效。白细胞介素-6 （IL-6）是心肌梗死释放的一种促炎细胞因子，与不良临床预后相关。Tocilizumab （TCZ）是一种针对IL-6受体的人源化单克隆抗体。在一项随机、双盲、安慰剂对照试验中，除了标准护理药物和干预措施外，我们为入院的MI患者分配了单次皮下剂量为162 mg的TCZ与安慰剂。主要结局是入组后30天主要不良心脏事件（MACE）的变化。次要结局评估入组后30天CRP的变化、QT/QTc的变化以及不良事件趋势的监测。由于受试者入组速度减慢，主要或次要结局均未发现趋势，因此进行了无效分析。共纳入28名受试者；12人服用TCZ， 16人服用安慰剂。在人口统计学、合并症或接受的医疗/介入治疗方面，研究组之间没有统计学上的显著差异。MACE差异无统计学意义。给予TCZ后CRP升高，但无统计学意义。没有观察到不良事件或安全信号。虽然无效分析表明，随着招募速度的减慢，主要结局不太可能实现，但我们没有观察到任何不良事件或安全趋势。基于这些信息，未来的研究应该进行，以评估TCZ作为心肌梗死辅助治疗的真正益处。本文报告的工作是在美国空军外科医生批准的临床研究FKE20140029下进行的，并已在ClinicalTrials.gov上注册，标识符为NCT02419937。
Acute myocardial infarction (MI) occurs when blood supply falls below critical levels and normal cellular maintenance mechanisms fail. Interleukin-6 (IL-6) is a proinflammatory cytokine released in MI and associated with poor clinical outcomes. Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor. In a randomized, double-blinded, placebo controlled trial we assigned subjects admitted with MI a single TCZ dose of 162 mg subcutaneously vs. placebo in addition to standard of care medications and interventions. Primary outcome was a change in major adverse cardiac events (MACE) 30 days after enrollment. Secondary outcomes assessed changes in CRP 30 days after enrollment, changes in QT/QTc, and monitoring for trends in adverse events. Futility analysis was performed as subject enrollment slowed and no trends were noted in either the primary or secondary outcomes. Twenty-eight subjects were enrolled; 12 to TCZ and 16 to placebo. No statistically significant differences were noted between study arms regarding demographics, comorbidities, or medical/interventional therapies received. No statistically significant differences in MACE were observed. CRP increased after administration of TCZ but this was not statistically significant. No adverse events or safety signals were observed. Though futility analysis suggested that the primary outcome was not likely achievable as our recruitment slowed, we did not observe any adverse events or safety trends. Building on this information, future studies should be conducted to assess a true benefit from TCZ as adjunct therapy for MI. The work reported herein was performed under United States Air Force Surgeon General approved Clinical Investigation FKE20140029 and has been registered at ClinicalTrials.gov under identifier NCT02419937.