Insights on Selected Procoagulation Markers and Outcomes in Stroke Trial (I-SPOT)

关于中风试验中选定的促凝标志物和结果的见解 (I-SPOT)

• 批准号: 8605239
• 负责人: NINA T GENTILE
• 金额: $ 47.94万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605239
• 关键词: Activities of Daily Living; Acute; Ancillary Study; Award; Binding; Biological Markers; Blood; Blood Coagulation Factor VII; Blood Glucose; Blood coagulation; Clinical; Clinical Pathways; Clinical Trials; Communities; Conduct Clinical Trials; Data; Disease; Emergency treatment; Factor VIIa; Fibrin fragment D; Funding; Generations; Glucose; Health Personnel; Hospitals; Hour; Hyperglycemia; Injury; Insulin; Intravenous; Ischemic Stroke; Measures; Membrane; National Institute of Neurological Disorders and Stroke; Neurologic; Neurological emergencies; Neurological outcome; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pathway interactions; Patients; Phase; Plasma; Plasminogen Activator Inhibitor 1; Randomized Controlled Trials; Recruitment Activity; Recurrence; Research Design; Research Project Grants; Risk; Safety; Severities; Stroke; TFPI; Thrombin; Thromboplastin; United States National Institutes of Health; Whole Blood; acute stroke; antithrombin III-protease complex; blood glucose regulation; design; functional outcomes; glycemic control; insight; primary outcome; prothrombin fragment 1.2; public health relevance; research study; response; standard care; stroke therapy; subcutaneous; treatment duration; treatment trial

DESCRIPTION (provided by applicant): Activation of the tissue factor (TF) pathway of blood coagulation is associated with increased blood thrombogenicity and increases in markers of blood coagulation levels may in part explain the high degree of poor neurological outcome and recurrence of stroke in patients with acute ischemic stroke (AIS). We have shown that membrane-bound tissue factor procoagulant activity (TF-PCA) and plasma activated factor VII (FVIIa) and markers of thrombin generation, prothrombin fragment 1.2 (F1.2) and thrombin- antithrombin complexes (TAT), are markedly elevated after AIS. While these markers are highest in patients with T2DM and hyperglycemia, the effect of blood glucose (BG) control on levels of blood coagulation markers and their relationship with stroke outcome is unknown. Therefore, a better understanding of the relationhips between these and other markers of blood coagulation and clinical outcomes after stroke and how hyperglycemia control modulates these markers holds great promise for management of acute ischemic stroke. The Insights on Selected Procoagulation Markers and Outcomes in Stroke Trial (I-SPOT): Response to Insulin Administration and Blood Glucose Control proposal is designed to accompany the Stroke Hyperglycemia Insulin Network Effort (SHINE) clinical trial, a Phase III multicenter, randomized, controlled trial planning to determine the efficacy an validate the safety of glycemic control in stroke patients. The SHINE trial will recruit 1,400 AIS patients with Type II diabetes mellitus (T2DM) and hyperglycemia, each receiving 3 days of hyperglycemia control with intravenous (IV) insulin therapy or control therapy with subcutaneous (SQ) insulin. Blood coagulation marker levels [whole blood TF-PCA~ plasma coagulation factors VII, VIIa, and VIII~ plasma TAT~ D-dimer~ tissue factor pathway inhibitor (TFPI)~ and plasminogen activator inhibitor-1 (PAI-1)] will be measured before and at 48 hours after the start of treatment. Baseline and temporal changes in biomarkers levels will be compared between treatment groups. The aims and hypotheses of the I-SPOT study are to 1) Compare the effects of strict hyperglycemia control with standard treatment of hyperglycemia on membrane- bound TF-PCA and markers of blood coagulation in T2DM patients after AIS and 2) Determine the relationship between circulating TF-PCA and markers of blood coagulation and functional neurological outcome in SHINE treatment and control patients. We anticipate that 1) the decrease in levels of markers of blood coagulation will be greater in patients treated with IV insulin to reduce BG than in patients treated with SQ Insulin as the standard fashion and 2) the decrease in levels of markers of blood coagulation will be greater in patients with than without favorable outcome (defined as the baseline stroke severity adjusted measure of functional ability at 90 days after acute stroke). Moreover, we expect that hyperglycemia control will modulate the relationship between blood coagulation levels and functional outcome in T2DM patients providing further insights on the effects of glucose regulation on the TF pathway of blood coagulation in acute stroke.

描述（由申请人提供）：血液凝血的组织因子（TF）途径的激活与血栓形成性的增加有关，并且血液凝血水平的标记物的增加可能部分解释了急性缺血性卒中患者的高度不良神经学结果和中风的复发程度。 我们已经表明，在AIS之后，AIS明显地升高了膜结合的组织因子（TF-PCA）和血浆激活因子VII（FVIIA）以及凝血酶产生的标志物，凝血酶原片段1.2（F1.2）和凝血酶 - 抗抑制剂复合物（TAT）。尽管这些标记在T2DM和高血糖患者中最高，但血糖（BG）控制对血液凝结标记水平的影响及其与中风结果的关系尚不清楚。因此，对这些标记和中风后的血液凝结和临床结局之间的关系以及高血糖控制如何调节这些标记的这些标记对这些标记的管理有很大的希望，可以更好地理解这些标记的急性缺血性中风。 对中风试验（I-SPOT）中选定的促进标记和结果的见解：对胰岛素给药和血糖控制建议的反应旨在伴随中风高血糖胰岛素网络努力（SHINE）临床试验，III期多中心，随机，对照试验，以确定效率的效率，以确定雅语的安全性。 Shine Trial将招募1,400 AI II型糖尿病（T2DM）和高血糖患者，每个患者均接受静脉内（IV）胰岛素治疗或皮下（SQ）胰岛素的治疗治疗3天的高血糖控制。血液凝血标记水平[全血TF-PCA〜等离子体凝结因子VII，VIIA和VIII〜PLASMA TAT〜D-DIMER〜组织因子因子途径抑制剂（TFPI）〜和纤溶酶原激活剂抑制剂-1（PAI-1）]将在治疗后的48小时之前进行测量。在治疗组之间将比较生物标志物水平的基线和时间变化。 I SPOT研究的目的和假设是1）比较严格的高血糖控制与高血糖的标准治疗对膜结合的TF-PCA的影响，以及AIS和2）在AIS和2）中T2DM患者的血液凝结标记和2）确定TF-PCA之间的关系，确定TF-PCA之间的关系与血液凝结和功能性神经学患者之间的关系。我们预计1）接受IV治疗的患者，血液凝结标记水平的降低会更大 胰岛素减少BG的胰岛素比用SQ胰岛素作为标准方式的患者和2）患者的血液凝结标记水平的降低要大于没有良好结果的患者（定义为急性中风后90天的基线中风严重程度调整了功能能力的措施）。此外，我们预计高血糖控制将调节T2DM患者的血液凝血水平与功能结果之间的关系，从而进一步见解葡萄糖调节对急性中风血液凝结的TF途径的影响。