The Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

描述(申请人提供)：由于中风是一种常见的、破坏性的和极其昂贵的疾病，因此对中风患者的改善治疗的需求越来越大。40%的急性缺血性中风患者到达医院时血糖都很高。高血糖与较差的临床结果相关，但严格的血糖控制是否能改善结果尚不清楚。严重或长期的低血糖也会对脑缺血造成很大的损害。临床平衡是存在的，目前美国心脏协会的指南鼓励临床试验，为如何治疗高血糖急性中风患者提供证据。SHARE试验是一项多中心、随机、单盲(双盲结果)III期试验，涉及全美56个地点的1,400名患者。患者将被随机分为血糖控制严格的静脉胰岛素组(80-130 mg/dL)和标准滑动比例皮下胰岛素组(&lt；180 mg/dL)。主要结果将是严重程度调整后的二分法改良Rankin评分(MRS)(响应者分析)。本试验的具体目的是：1.明确目标1：根据MRS在卒中后90天的MRS测量结果，确定高血糖急性缺血性卒中患者在症状出现12小时内(到达ED后3小时内)，将血糖控制在80-130 mg/dL的目标范围内静脉注射胰岛素的疗效。假设1：严格的血糖控制(目标80-130 mg/dL)，与对照组相比，使用eProtoin-Insulin的静脉胰岛素输注疗法将使严重程度调整后的90天MRS的有利结果增加7%或更多。具体目的2：确定高血糖急性缺血性卒中患者接受高血糖急性缺血性卒中治疗72小时后严格血糖控制和静脉注射胰岛素的安全性。假设2：根据严重低血糖发生率(40 mg/dL)不到4%来确定，使用eProtoin-Ins的静脉注射胰岛素治疗严格的血糖控制是安全的。

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%.