Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, England.
Stroke, Nottingham University Hospitals NHS Trust, Nottingham, England.
JAMA Neurol. 2020 Jan 1;77(1):114-124. doi: 10.1001/jamaneurol.2019.4107.
While there are a limited number of beneficial treatments for acute stroke (eg, stroke units, reperfusion, aspirin, hemicraniectomy), there are more negative (as opposed to neutral) interventions spanning multiple different mechanisms of action. To reduce the risk of future negative studies, it is vital to understand why previous interventions appeared to cause harm.
The limited number of beneficial treatments for acute ischemic stroke are far outnumbered by negative (not neutral) interventions that worsened outcomes in randomized clinical trials (RCTs), including those with putative neuroprotectant, anticoagulant, anti-inflammatory, free radical-scavenging, hemorrhagic, or vasoactive activity. Other agents reduced thrombolytic efficiency or exhibited neuropsychiatric or cardiac toxicity. In intracerebral hemorrhage, platelet transfusion was hazardous. Although reperfusion treatments should be given as soon as possible, very early intervention with other strategies may instead be hazardous, as has been seen with physical therapy and vasodepressors.
The lessons learned from negative stroke RCTs are vital for designing future studies. Multicenter preclinical studies are necessary, and animals that die must be included in analyses. Randomized clinical trials must assess multiple neurological, vascular, cardiac, and general safety effects, whether these are on target or off target. All preclinical trials and RCTs must be published in full. Learning from the past will help to reduce the number of negative stroke RCTs in the future.
尽管急性中风（例如中风病房、再灌注、阿司匹林、半脑切除术）的有效治疗方法有限，但跨越多种不同作用机制的负面（而非中性）干预措施更多。为了降低未来负面研究的风险，了解先前的干预措施为何似乎造成伤害至关重要。
在随机临床试验（RCT）中，急性缺血性中风的有效治疗方法数量有限，远远少于负面（而非中性）干预措施，这些干预措施使结果恶化，包括具有假定神经保护、抗凝、抗炎、自由基清除、出血或血管活性作用的干预措施。其他药物降低了溶栓效率或表现出神经精神或心脏毒性。在脑出血中，血小板输注是危险的。尽管再灌注治疗应尽快进行，但其他策略的早期干预可能会造成危害，如物理治疗和血管舒张剂的情况。
从负面中风 RCT 中吸取的教训对于设计未来的研究至关重要。需要进行多中心临床前研究，并且必须将死亡的动物纳入分析中。随机临床试验必须评估多个神经、血管、心脏和一般安全性影响，无论这些影响是否针对目标或非目标。所有临床前试验和 RCT 都必须完整发表。从过去的经验中学习将有助于减少未来负面中风 RCT 的数量。
