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、毁灭性的、极其昂贵的疾病，对中风患者的治疗方法的需求日益增加。40%的急性缺血性中风患者在被送到医院时患有高血糖。高血糖与较差的临床预后相关，但严格的血糖控制是否能改善预后尚不清楚。严重或长期的低血糖也会对缺血的大脑造成很大的损害。临床平衡是存在的，目前的美国心脏协会指南鼓励临床试验为如何治疗高血糖急性卒中患者提供证据。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。患者将随机分为血糖严格控制的静脉注射胰岛素组（80-130 mg/dL）和标准滑动刻度皮下胰岛素组（<180 mg/dL）。主要结局将是严重程度调整后的二分类修正兰金评分（mRS）（应答者分析）。该试验的具体目标是：“具体目标1：确定在卒中后90天的mr测量中，在症状出现12小时（到达ED 3小时）内，高血糖急性缺血性卒中患者静脉注射胰岛素将血糖严格控制在80-130 mg/dL的目标范围内的疗效。”假设1：与对照组相比，使用eProtocol-insulin（一种经过验证的计算机决策支持工具）进行静脉胰岛素输注治疗的严格血糖控制（目标80-130 mg/dL）将使经严重程度调整的90天mr有利结果绝对提高7%或更多。特异性目的2：确定静脉注射胰岛素对治疗72小时的高血糖急性缺血性脑卒中患者严格控制血糖的安全性。假设2：严格控制血糖，使用eprotocol -胰岛素输注治疗是安全的，严重低血糖率（< 40mg /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%.