c-FN as a predictor of hemorrhagic transformation in t-PA treated stroke patients

c-FN 作为 t-PA 治疗中风患者出血性转化的预测因子

• 批准号: 7220477
• 负责人: Albert K Man
• 金额: $ 20.62万
• 依托单位: PREDICTION SCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220477
• 关键词: Accounting; Acute; Admission activity; Adult; Adverse effects; Affect; Age; Alteplase; American; Americas; Apolipoproteins C; Biological Assay; Biological Markers; Biological Neural Networks; Blood Clot; Blood coagulation; Brain; Cause of Death; Characteristics; Classification; Clinical; Clinical Data; Coagulation Process; Contracts; Data; Data Set; Development; Diagnosis; Diagnostic; Discriminant Analysis; Discrimination; Disease regression; Economic Burden; Elevation; Enzyme-Linked Immunosorbent Assay; Evolution; Facilities and Administrative Costs; Fibronectins; Fright; Future; Guidelines; Health Care Costs; Hemorrhage; Hour; Image Analysis; Incidence; Institutes; Institution; Ischemic Stroke; Life; Machine Learning; Manufacturer Name; Measures; Metalloproteases; Modeling; Molecular; Non-linear Models; Outcome; Patients; Pharmaceutical Preparations; Phase; Physicians; Physiological reperfusion; Plasma; Predictive Factor; Publications; Purpose; Recording of previous events; Recovery; Reperfusion Therapy; Reporting; Reproducibility; Research; Risk; Safety; Sampling; Science; Sensitivity and Specificity; Serum amyloid A protein; Severities; Societies; Statistically Significant; Stroke; Technology; Testing; Thrombolytic Therapy; Time; Treatment outcome; Trees; United States Food and Drug Administration; Validation; Vascular blood supply; apolipoprotein C-III; base; brain tissue; desire; disability; falls; follow-up; improved; nervous system disorder; point of care; prognostic; social; statistics; tool; validation studies

DESCRIPTION (provided by applicant): Currently there is only one approved drug treatment for acute ischemic stroke, t-PA. t-PA is a highly beneficial treatment but is severely underutilized due largely to fear of an often fatal side effect called hemorrhagic transformation. There is a critical clinical need for a diagnostic to identify patients that are at high and low risk of hemorrhagic transformation (HT). A preliminary study showed that plasma level of cellular fibronectin (c-Fn) was predictive of t-PA induced HT. We will collect patient samples and perform a validation study to confirm the utility of c-Fn as a molecular diagnostic for the prediction of more severe forms of HT. In this study we will determine the threshold levels of c-Fn that are most predictive of outcome, determine if the elevation of c-Fn is time dependant, and follow c-Fn levels through treatment. In addition we will analyze additional plasma biomarkers, matrix metalloprotease 9 (MMP9), apolipoprotein C-III (Apo-C), and serum amyloid A (SAA) as potential contributors to c-Fn to more accurately predict HT. A successful diagnostic would greatly improve safety and increase use of t-PA/thrombolytics in the treatment of stroke. This validation study develops the first biomarker-based diagnostic to aid physicians in the identification of patients with high and low risk of bleeding as a result of clot busting treatment of acute ischemic stroke. Successful development will increase safety and usage of this highly beneficial treatment as well as lower overall healthcare cost as a result of stroke.

描述（由申请人提供）：目前只有一种批准的治疗急性缺血性中风的药物，t-PA。 t-PA 是一种非常有益的治疗方法，但严重未得到充分利用，主要是因为担心一种经常致命的副作用，即出血性转化。临床迫切需要通过诊断来识别出血性转化 (HT) 高风险和低风险的患者。初步研究表明，细胞纤连蛋白 (c-Fn) 的血浆水平可预测 t-PA 诱导的 HT。我们将收集患者样本并进行验证研究，以确认 c-Fn 作为分子诊断来预测更严重形式的 HT 的效用。在本研究中，我们将确定最能预测结果的 c-Fn 阈值水平，确定 c-Fn 的升高是否具有时间依赖性，并通过治疗跟踪 c-Fn 水平。此外，我们将分析其他血浆生物标志物、基质金属蛋白酶 9 (MMP9)、载脂蛋白 C-III (Apo-C) 和血清淀粉样蛋白 A (SAA) 作为 c-Fn 的潜在贡献者，以更准确地预测 HT。成功的诊断将大大提高安全性并增加 t-PA/溶栓剂在中风治疗中的使用。这项验证研究开发了第一个基于生物标志物的诊断，以帮助医生识别因急性缺血性中风的溶栓治疗而导致出血风险高和低的患者。成功的开发将提高这种非常有益的治疗方法的安全性和使用率，并降低中风导致的总体医疗费用。