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: 9208166
• 负责人: NINA T GENTILE
• 金额: $ 39.37万
• 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 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9208166
• 关键词: Activities of Daily Living; Acute; Ancillary Study; Award; Biological Markers; Blood; Blood Coagulation Factor VII; Blood Glucose; Blood coagulation; Clinical; Clinical Trials; Communities; Conduct Clinical Trials; Data; Disease; 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; Risk; Safety; Severities; Spottings; Stroke; TFPI; Thrombin; Thromboplastin; United States National Institutes of Health; Whole Blood; activity marker; acute stroke; antithrombin III-protease complex; blood glucose regulation; design; functional outcomes; glycemic control; insight; primary outcome; programs; prothrombin fragment 1; public health relevance; research study; response; standard care; stroke therapy; subcutaneous; treatment duration; treatment group; 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）：凝血组织因子（TF）途径的激活与血栓形成性增加有关，并且凝血水平标志物的增加可能部分解释了患者神经系统结果严重不良和中风复发的原因患有急性缺血性中风（AIS）。 我们发现膜结合组织因子促凝血活性 (TF-PCA) 和血浆活化因子 VII (FVIIa) 以及凝血酶生成标记物、凝血酶原片段 1.2 (F1.2) 和凝血酶-抗凝血酶复合物 (TAT) 显着升高AIS 之后。虽然这些标志物在 T2DM 和高血糖患者中最高，但血糖 (BG) 控制对凝血标志物水平的影响及其与中风结果的关系尚不清楚。因此，更好地了解这些和其他凝血标志物与中风后临床结果之间的关系，以及高血糖控制如何调节这些标志物，为急性缺血性中风的治疗带来了巨大希望。 关于中风试验中选定的促凝血标志物和结果的见解 (I-SPOT)：对胰岛素给药和血糖控制提案的反应旨在配合中风高血糖胰岛素网络努力 (SHINE) 临床试验，这是一项 III 期多中心、随机、对照试验试验计划以确定中风患者血糖控制的有效性和安全性。 SHINE 试验将招募 1,400 名 AIS 患有 II 型糖尿病 (T2DM) 和高血糖的患者，每人接受 3 天的静脉注射 (IV) 胰岛素治疗或皮下 (SQ) 胰岛素控制治疗的高血糖控制。凝血标志物水平[全血TF-PCA~血浆凝血因子VII、VIIa和VIII~血浆TAT~D-二聚体~组织因子途径抑制剂（TFPI）~和纤溶酶原激活剂抑制剂-1（PAI-1）]在治疗开始前和治疗开始后 48 小时进行测量。将比较治疗组之间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) 比较严格高血糖控制与标准高血糖治疗对 AIS 后 T2DM 患者膜结合 TF-PCA 和凝血标志物的影响，2) 确定两者之间的关系SHINE 治疗和对照患者的循环 TF-PCA 以及凝血标志物和功能性神经系统结果。我们预计 1) 接受静脉注射治疗的患者的凝血标志物水平下降幅度会更大 与接受 SQ 胰岛素治疗的患者相比，使用胰岛素可降低 BG 作为标准方式，并且 2) 与没有良好结果的患者相比，凝血标志物水平的下降幅度更大（定义为基线中风严重程度调整后的功能能力测量）急性中风后 90 天）。此外，我们预计高血糖控制将调节 T2DM 患者的凝血水平和功能结果之间的关系，从而进一步了解葡萄糖调节对急性卒中凝血的 TF 途径的影响。

项目成果

Coagulation markers and functional outcome in acute ischemic stroke: Impact of intensive versus standard hyperglycemia control.

急性缺血性中风的凝血标志物和功能结果：强化与标准高血糖控制的影响。

• 发表时间: 2021-07
• 作者: Gentile, Nina T;Rao, A Koneti;Reimer, Hannah;Del Carpio;Ramakrishnan, Viswanathan;Pauls, Qi;Barsan, William G;Bruno, Askiel;iSPOT, Neurological Emergencies Treatment Trials Network (NETT) Investigators
• 通讯作者: iSPOT, Neurological Emergencies Treatment Trials Network (NETT) Investigators