2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649605摘要：研究立論基礎：高血糖是急性腦中風病患常見的併發症。過去許多的研究已經證實中風後24 小時仍持續高血糖的患者，相較於正常血糖患者有較差的預後。但針對急性腦中風合併高血糖患者，如何能夠有效的控制血糖並能達到較好的預後仍未確定。研究目的：本研究為多中心的隨機分配試驗，針對入住加護病房的急性中風併高血糖患者，比較使用皮下注射一天一次的長效胰島素（insulin glargine，甘精胰島素），或以多次注射短效胰島素（regular insulin）為主的血糖控制流程，在中風急性期的有效及安全性。研究設計：本研究為三年期、隨機分配的多中心試驗計畫。預計納入約120 位急性腦中風合併高血糖的患者，在中風發生後24 小時內根據事前設計好的劑量相應增減對照表（sliding scale），分成(a)皮下注射一天一次生理劑量的長效胰島素並於急性血糖升高時給予短效胰島素或(b)每餐前使用短效胰島素並於開始以口進食後，睡前給予中長效胰島素（NPH）兩組。試驗期間為加護病房入住後72 小時。受試者的納入條件為急性腦中風於發病後24 小時內入住加護病房，於間隔兩小時的血糖測試皆超過200 mg/dL。排除條件包括年齡小於20 歲、懷孕、休克、嚴重感染、即將需要手術、立即有生命危險、末期腎病需要透析、第一型糖尿病及正在使用類固醇患者。試驗期間每四小時檢驗微血管血糖濃度，以調整下次胰島素施打劑量。本研究也會使用連續性血糖監測系統來分析試驗期間的血糖相關指標。此外，受試期間每天會收集10 毫升血液及24 小時尿液來檢驗血中相關發炎生物指標及尿中兒茶酚胺激素濃度。研究預後指標：本研究的主要指標為試驗期間血糖數值在80至180 mg/dL範圍內的比率。次要指標包括：(1)中風後三個月的功能性預後為良好的比例(定義為雷氏修正量表小於等於兩分)；(2)急性期中風惡化的比例；(3)根據連續性血糖監測系統的數據，分析試驗期間的24小時血糖變異程度；(4)血中及尿液的相關生物指標。整體而言：本研究可能對於臨床上處置急性腦中風併高血糖患者提供重要且新的治療資訊，尤其是在急性腦中風早期給予長效胰島素(insulin glargine)的可能益處及風險。<br> Abstract: Study Rationale: Hyperglycemia is common during acute ischemic stroke. It has been shownthat persistent in-hospital hyperglycemia during the first 24 hours (h) after stroke is associatedwith worse outcomes than normoglycemia. However, the optimal strategy to controlhyperglycemia during acute ischemic stroke has not been established.Aims: The object of this multicenter randomized controlled study is to determine the efficacyand safety of early initiation of subcutaneous once-daily insulin glargine, in comparison withregular insulin, based on a protocolized sliding scale regimen to achieve proper sugar controlin acute stroke patients with hyperglycemia admitted to the intensive care unit (ICU).Design: This is a 3-year, randomized, multicenter trial. Approximate 120 hyperglycemicacutestroke patients who will receive either (a) subcutaneous long acting basal insulin (insulinglargine) with added short acting regular insulin to correct hyperglycemic events or (b) shortacting regular insulin pre-meal with added NPH at bed time if start eating, for 72 h, startingwithin 24 h of stroke symptom onset. The inclusion criteria are patients who admitted tostroke ICU within 24 hours of acute stroke onset and have repeated random blood glucose>200 mg/dL with a 2 hours interval. The exclusion criteria include patients with age <20years, pregnancy, shock, severe infection, end stage renal disease requiring dialysis, type IDM or current steroid usage. Capillary blood glucose will be measured every 4-hours toadjust the next insulin dose. Glucometric parameters willalso be analyzed by continuousblood glucose monitoring system. 10 ml blood and same amount of urine from 24 hours urinecollection will be collected every day for further measurement of a variety of bloodinflammatory markers and urine catecholamine levels.Study outcomes: The primary endpoint is thepercentage of time in the range of 80-180 mg/dLduring the sugar monitoring period. The secondary endpoints include: (1) good functionaloutcome at 3 months post stroke (modified Rankin Scale <2), (2) stroke in evolution, (3) 24hours blood glucose variability via continuous glucose monitoring, and (4) blood and urinebiomarkers.In summary, this trial will provide important novel information about preferred managementof acute ischemic stroke patients with hyperglycemia. It will determine the potential benefitsand risks of application of long acting basal insulin during very early stage of acute stroke.研究立論基礎：高血糖是急性腦中風病患常見的併發症。過去許多的研究已經證實中風 後24 小時仍持續高血糖的患者，相較於正常血糖患者有較差的預後。但針對急性腦中 風合併高血糖患者，如何能夠有效的控制血糖並能達到較好的預後仍未確定。 研究目的：本研究為多中心的隨機分配試驗，針對入住加護病房的急性中風併高血糖患 者，比較使用皮下注射一天一次的長效胰島素（insulin glargine，甘精胰島素），或以多 次注射短效胰島素（regular insulin）為主的血糖控制流程，在中風急性期的有效及安全 性。 研究設計：本研究為三年期、隨機分配的多中心試驗計畫。預計納入約120 位急性腦中 風合併高血糖的患者，在中風發生後24 小時內根據事前設計好的劑量相應增減對照表 （sliding scale），分成(a)皮下注射一天一次生理劑量的長效胰島素並於急性血糖升高時 給予短效胰島素或(b)每餐前使用短效胰島素並於開始以口進食後，睡前給予中長效胰島 素（NPH）兩組。試驗期間為加護病房入住後72 小時。受試者的納入條件為急性腦中 風於發病後24 小時內入住加護病房，於間隔兩小時的血糖測試皆超過200 mg/dL。排除 條件包括年齡小於20 歲、懷孕、休克、嚴重感染、即將需要手術、立即有生命危險、 末期腎病需要透析、第一型糖尿病及正在使用類固醇患者。試驗期間每四小時檢驗微血 管血糖濃度，以調整下次胰島素施打劑量。本研究也會使用連續性血糖監測系統來分析 試驗期間的血糖相關指標。此外，受試期間每天會收集10 毫升血液及24 小時尿液來檢 驗血中相關發炎生物指標及尿中兒茶酚胺激素濃度。 研究預後指標：本研究的主要指標為試驗期間血糖數值在80至180 mg/dL範圍內的比率。 次要指標包括：(1)中風後三個月的功能性預後為良好的比例(定義為雷氏修正量表小於 等於兩分)；(2)急性期中風惡化的比例；(3)根據連續性血糖監測系統的數據，分析試驗 期間的24小時血糖變異程度；(4)血中及尿液的相關生物指標。 整體而言：本研究可能對於臨床上處置急性腦中風併高血糖患者提供重要且新的治療資 訊，尤其是在急性腦中風早期給予長效胰島素(insulin glargine)的可能益處及風險。Study Rationale: Hyperglycemia is common during acute ischemic stroke. It has been shown that persistent in-hospital hyperglycemia during the first 24 hours (h) after stroke is associated with worse outcomes than normoglycemia. However, the optimal strategy to control hyperglycemia during acute ischemic stroke has not been established. Aims: The object of this multicenter randomized controlled study is to determine the efficacy and safety of early initiation of subcutaneous once-daily insulin glargine, in comparison with regular insulin, based on a protocolized sliding scale regimen to achieve proper sugar control in acute stroke patients with hyperglycemia admitted to the intensive care unit (ICU). Design: This is a 3-year, randomized, multicenter trial. Approximate 120 hyperglycemicacute stroke patients who will receive either (a) subcutaneous long acting basal insulin (insulin glargine) with added short acting regular insulin to correct hyperglycemic events or (b) short acting regular insulin pre-meal with added NPH at bed time if start eating, for 72 h, starting within 24 h of stroke symptom onset. The inclusion criteria are patients who admitted to stroke ICU within 24 hours of acute stroke onset and have repeated random blood glucose >200 mg/dL with a 2 hours interval. The exclusion criteria include patients with age <20 years, pregnancy, shock, severe infection, end stage renal disease requiring dialysis, type I DM or current steroid usage. Capillary blood glucose will be measured every 4-hours to adjust the next insulin dose. Glucometric parameters willalso be analyzed by continuous blood glucose monitoring system. 10 ml blood and same amount of urine from 24 hours urine collection will be collected every day for further measurement of a variety of blood inflammatory markers and urine catecholamine levels. Study outcomes: The primary endpoint is thepercentage of time in the range of 80-180 mg/dL during the sugar monitoring period. The secondary endpoints include: (1) good functional outcome at 3 months post stroke (modified Rankin Scale <2), (2) stroke in evolution, (3) 24 hours blood glucose variability via continuous glucose monitoring, and (4) blood and urine biomarkers. In summary, this trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of application of long acting basal insulin during very early stage of acute stroke.急性中風高血糖長效胰島素短效胰島素acute strokehyperglycemiainsulin glargineregular insulin