Abstract：
Cerebral small vessel disease (cSVD) causes lacunar stroke (25% of ischaemic strokes), haemorrhage, dementia, physical frailty, or is \'covert\', but has no specific treatment. Uncertainties about the design of clinical trials in cSVD, which patients to include or outcomes to assess, may have delayed progress. Based on experience in recent cSVD trials, we reviewed ways to facilitate future trials in patients with cSVD.We assessed the literature and the LACunar Intervention Trial 2 (LACI-2) for data to inform choice of Participant, Intervention, Comparator, Outcome, including clinical versus intermediary endpoints, potential interventions, effect of outcome on missing data, methods to aid retention and reduce data loss. We modelled risk of missing outcomes by baseline prognostic variables in LACI-2 using binary logistic regression.Imaging versus clinical outcomes led to larger proportions of missing data. We present reasons for and against broad versus narrow entry criteria. We identified numerous repurposable drugs with relevant modes of action to test in various cSVD subtypes. Cognitive impairment is the most common clinical outcome after lacunar ischaemic stroke but was missing more frequently than dependency, quality of life or vascular events in LACI-2. Assessing cognitive status using Diagnostic and Statistical Manual for Mental Disorders Fifth Edition can use cognitive data from multiple sources and may help reduce data losses.Trials in patients with all cSVD subtypes are urgently needed and should use broad entry criteria and clinical outcomes and focus on ways to maximise collection of cognitive outcomes to avoid missing data.
摘要：
脑小血管病（cSVD）导致腔隙性卒中（25%的缺血性卒中），出血,痴呆症,身体虚弱,或者是\'隐蔽\'，但没有具体的治疗方法.cSVD临床试验设计的不确定性，包括哪些患者或评估哪些结果，可能会延迟进展。根据最近cSVD试验的经验，我们回顾了促进cSVD患者未来试验的方法.我们评估了文献和LACunar干预试验2（LACI-2）的数据，以告知参与者的选择，干预,比较器,结果,包括临床终点和中间终点，潜在的干预措施，结果对缺失数据的影响，帮助保留和减少数据丢失的方法。我们使用二元逻辑回归通过LACI-2中的基线预后变量对缺失结果的风险进行建模。与临床结果相比，影像学导致了更大比例的数据缺失。我们提出了赞成和反对广义和狭义进入标准的理由。我们确定了许多具有相关作用模式的可再利用药物，以测试各种cSVD亚型。认知损害是腔隙性缺血性卒中后最常见的临床结局，但缺失的频率高于依赖性。LACI-2的生活质量或血管事件。使用精神障碍诊断和统计手册第五版评估认知状态可以使用来自多个来源的认知数据，并可能有助于减少数据丢失。迫切需要对所有cSVD亚型患者进行试验，应使用广泛的进入标准和临床结果，并着重于最大程度地收集认知结果以避免数据缺失的方法。
