The Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

描述（由申请人提供）：由于中风是一种常见的、破坏性的和对医疗保健系统极其昂贵的疾病，因此越来越需要改善中风患者的治疗。40%的急性缺血性中风患者在到达医院时是高血糖的。高血糖与较差的临床结局相关，但尚不清楚严格的血糖控制是否能改善结局。严重或长时间的低血糖也可能对缺血性大脑造成严重损害。临床平衡存在，目前的美国心脏协会指南鼓励临床试验提供如何治疗高血糖急性卒中患者的证据。SHINE试验是一项多中心、随机、单盲（双盲结果）III期试验，在美国56个地点的1400名患者中进行。患者将被随机分配至IV胰岛素组（严格血糖控制（80-130 mg/dL））和标准滑动标度皮下胰岛素组（<180 mg/dL）。主要结局将是严重程度调整的二分改良兰金评分（mRS）（应答者分析）。本试验的具体目的是：“具体目的1：确定高血糖急性缺血性卒中患者在症状发作后12小时内（以及到达艾德后3小时）通过静脉输注胰岛素将血糖严格控制在80-130 mg/dL的目标范围的疗效，如卒中后90天通过mRS测量的。假设1：与对照组相比，使用eProtocol-insulin（一种经验证的计算机化决策支持工具）进行IV胰岛素输注治疗的严格血糖控制（目标80-130 mg/dL）将使mRS上严重程度调整后的90天有利结局增加绝对7%或更多。具体目标二：在高血糖急性缺血性卒中患者中，通过静脉输注胰岛素来严格控制血糖，治疗时间长达72小时，确定其安全性。假设二：通过使用eProtocol-insulin的IV胰岛素输注治疗进行严格的血糖控制是安全的，因为严重低血糖发生率（<40 mg/dL）小于4%。

DESCRIPTION (provided by applicant): There is an increasing need for improved treatments for stroke patients as stroke is a common, devastating and extremely costly disease to the health care system. Forty percent of acute ischemic stroke patients are hyperglycemic upon arrival to the hospital. Hyperglycemia is associated with worse clinical outcome but it is unclear if tight glucose control can improve outcome. Severe or prolonged hypoglycemia can also be very damaging to ischemic brain. Clinical equipoise exists and current American Heart Association Guidelines encourage clinical trials to provide evidence on how to treat hyperglycemic acute stroke patients. The SHINE Trial is a multicenter, randomized, single blind (double blind outcomes) Phase III trial of 1400 patients at 56 sites across the United States. Patients will be randomized to IV insulin with tight glucose control (80-130 mg/dL) versus standard sliding scale subcutaneous insulin (<180 mg/dL). The primary outcome will be a severity adjusted dichotomized modified Rankin score (mRS) (responder analysis). The specific aims for this trial are: ' Specific Aim 1: To determine the efficacy of tight glucose control to a target range of 80-130 mg/dL with IV insulin infusion in hyperglycemic acute ischemic stroke patients within 12 hours of symptom onset (and 3 hours of arrival to ED) as measured by mRS at 90 days after stroke. Hypothesis 1: Tight glucose control (target 80-130 mg/dL) with IV insulin infusion therapy using eProtocol-insulin, a validated computerized decision support tool, will increase the severity adjusted 90 day favorable outcome on the mRS by an absolute 7% or more, as compared to the control group. Specific Aim 2: To determine the safety of tight glucose control with IV insulin infusion in hyperglycemic acute ischemic stroke patients treated for up to 72 hrs. Hypothesis 2: Tight glucose control with IV insulin infusion therapy using eProtocol-insulin is safe as determined by a severe hypoglycemia rate (<40 mg/dL) of less than 4%.