CLEAR IVH Phase III Planning Grant

CLEAR IVH 第三期规划补助金

• 批准号: 7409940
• 负责人: DANIEL F HANLEY
• 金额: $ 16.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409940
• 关键词: Adverse event; Alteplase; Animal Model; Award; Biometry; Blinded; Blood; Brain hemorrhage; Caring; Case Report Form; Categories; Cerebral hemisphere hemorrhage; Certification; Clinical; Clinical Trials; Coagulation Process; Collection; Communities; Competence; Comprehension; Conscious; Data; Data Collection; Disease; Dose; Double-Blind Method; Drainage procedure; Drug Kinetics; Education; Effectiveness; Elderly woman; Electronics; End Point; Enrollment; Evaluation; Excision; Exposure to; Funding; Glasgow Outcome Scale; Goals; Grant; Guidelines; Hemorrhage; Hospitalization; Hospitals; Hour; Human; Image; Infection; Injury; Internet; Intervention; Intraventricular; Investigation; Label; Leadership; Length of Stay; Life; Literature; Location; Manuals; Measurement; Measures; Medical; Minority; Monitor; Morbidity - disease rate; Multicenter Trials; Neurologic; Numbers; Obstruction; Odds Ratio; Online Systems; Operative Surgical Procedures; Outcome; Outcome Measure; Patients; Peer Review; Performance; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physiological; Placebo Control; Population; Positioning Attribute; Procedures; Program Evaluation; Protocol Compliance; Protocols documentation; Quality of life; Randomized; Randomized Clinical Trials; Range; Rate; Reading; Recording of previous events; Recruitment Activity; Reporting; Request for Applications; Research Personnel; Residual state; Safety; San Francisco; Score; Screening procedure; Secure; Signal Transduction; Site; Standardization; Standards of Weights and Measures; Stroke; Survivors; Testing; Tissues; Training; Translating; Treatment Protocols; Week; brain tissue; concept; data management; day; demographics; falls; functional outcomes; health disparity; health related quality of life; improved; indexing; intraventricular hemorrhage; medical complication; mortality; programs; response; symposium; thrombolysis; treatment duration; trend; virtual

DESCRIPTION (provided by applicant): Brain hemorrhage is the most fatal form of stroke. For patients with both intracerebral (ICH) and intraventricular (IVH) hemorrhages, community mortality is consistently reported at 50-80% with no validated, efficacious treatment. Animal models demonstrate substantial physiologic and functional benefit when blood is removed rapidly from the ventricle; our human trial data show similar mortality and functional benefit trends with blood removal. Current therapy which uses extraventricular drainage (EVD) neither improves long-term survival nor alters the effect of blood on tissue. Adding recombinant tissue plasminogen activator (rt-PA) may be the key to a rapid, effective, and safe means for blood removal that limits brain tissue injury, increases the effectiveness of EVD's in removing blood and perhaps controlling ICP. If validated by a clinical trial, our therapy would offer the first-ever clinically directive intervention for this lethal disease. We seek support for a Phase III RCT trial using EVD and rt-PA as IVH treatment. New human safety and dose-finding data demonstrate the concept that rapid removal of IVH clot can be associated with clinically important improvements in morbidity and mortality. This is a strong signal that we can translate IVH animal models to human treatment with robust beneficial effects on level of consciousness, ICU treatment intensity, survival, and lowered neurologic morbidity burden as measured by functional performance. The literature, our data, and prior NINDS ICH and NINDS health disparities reviews, support the need for a pivotal Phase III trial, investigating the benefits of removal of IVH clot by comparing use of EVD plus rt-PA vs. EVD alone. We can potentially save lives and improve outcome of brain hemorrhage survivors which now disproportionately burdens minorities, women and the elderly. Once we provide critical evidence, generalization to a wide range of hospitals, using SPOTRIAS and newer networks, would be technically straightforward as the interventions and expertise to perform this therapy are already widespread. The planning grant will support a smooth transition from our Phase II trials which will be completed in the fall of 2007, to the definitive Phase III trial making us fully operational and in position to perform without delay.

描述（由申请人提供）：脑出血是最致命的中风形式。对于同时患有脑内 (ICH) 和脑室内 (IVH) 出血的患者，社区死亡率一致报告为 50-80%，且没有经过验证的有效治疗方法。动物模型显示，当血液从心室快速排出时，可带来显着的生理和功能益处；我们的人体试验数据显示，与除血相似的死亡率和功能益处趋势。目前使用脑室外引流（EVD）的疗法既不能改善长期生存，也不能改变血液对组织的影响。添加重组组织纤溶酶原激活剂 (rt-PA) 可能是快速、有效且安全的除血方法的关键，可限制脑组织损伤，提高 EVD 除血的有效性，并可能控制 ICP。如果通过临床试验得到验证，我们的疗法将为这种致命疾病提供有史以来第一个临床指导干预措施。我们寻求支持使用 EVD 和 rt-PA 作为 IVH 治疗的 III 期 RCT 试验。新的人体安全和剂量探索数据证明了这样的概念：快速去除 IVH 凝块可能与临床上发病率和死亡率的重要改善相关。这是一个强烈的信号，表明我们可以将 IVH 动物模型转化为人类治疗，对意识水平、ICU 治疗强度、生存率和降低神经系统发病负担（通过功能表现衡量）产生强大的有益影响。文献、我们的数据以及之前的 NINDS ICH 和 NINDS 健康差异审查支持进行关键 III 期试验的必要性，通过比较使用 EVD 加 rt-PA 与单独使用 EVD 来研究去除 IVH 血栓的益处。我们有可能拯救生命并改善脑出血幸存者的预后，脑出血幸存者现在给少数族裔、妇女和老年人带来了不成比例的负担。一旦我们提供了关键证据，使用 SPOTRIAS 和更新的网络，推广到广泛的医院在技术上就会很简单，因为执行这种疗法的干预措施和专业知识已经广泛存在。规划拨款将支持我们从 2007 年秋季完成的第二阶段试验到最终的第三阶段试验的顺利过渡，使我们能够全面运作并立即执行。