RANDOMIZED TRIAL OF ORG 10172 IN ACUTE ISCHEMIC STROKE

这是一个大型多中心，双- 盲态、安慰剂对照试验，采用意向治疗分析， 正在测试不含肝素的硫酸盐混合物 糖胺聚糖（类肝素/达那帕洛尔/CYP 10172），以改善 急性缺血性卒中患者中的重要结局事件。这 试验已在赠款5-R 0 -1-NS-27863-02下获得资助， 与R.F.Woolson（5- RO-1-NS-27960-01）。这两项建议将供联合审查。的 本试验中检验的主要假设是， 与常规医疗护理的结合上级联合 常规医疗和安慰剂在改善 中风后三个月的预后良好 抗血栓药物已用于患者的早期管理 患有急性缺血性中风超过50年这些药物是在 预防复发性栓塞、血栓形成进展或失败 侧支循环这些药物也可能是一种重要的辅助药物， 血栓溶解疗法。尽管它们被广泛使用， 关于其有效性和安全性的争议很大。的争议 这主要是由于缺乏任何数据支持的迹象， 或禁忌症。肝素的复杂性在于 严重的出血性副作用和血小板减少症。 低分子 体重抗血栓药物，如抗血栓药物10172可能比 常规肝素。 10172用于预防静脉 血栓形成和治疗肝素诱导的血小板减少症。试点研究 在急性缺血性卒中患者中， 这些数据被用于开发目前正在进行的试验。 这项精心设计和进行的试验于1990年1月获得资助。 到目前为止，研究人员已经招募了650多名患者， 计划在26个参与中心进行1300例。审判被 成功招募女性和少数民族作为试验对象。 有关审判的一些出版物已经出现。这些 论文报告了我们对进行试验的方法的开发和测试 和一些基线数据。该试验最近进行了中期研究 分析和我们的NINDS安全和监测委员会授权我们 继续招募和治疗患者。 当时， 中期分析超过99%的预期数据已输入我们的 数据系统 虽然我们在招聘方面落后，部分原因是 长期的监管和行政拖延，我们可以实现我们的目标， 来完成这个试验我们请求批准并继续提供资金 来完成这一重要的审判未来的审判， 这一规模和范围将检验急性中风的抗血栓治疗。

This is an application for continuation of a large multi-center, double- blind, placebo-controlled trial, using intention-to-treat analyses, that is testing the ability of the non-heparin containing mixture of sulfated glycosaminoglycurans (heparinoid/danaparolol/Org 10172) to improve important outcome events among patients with acute ischemic stroke. This trial has been funded under grant 5-R0-1-NS-27863-02 and is being submitted in conjunction with the continuing proposal by R.F.Woolson (5- R0-l-NS-27960-01). The two proposals are intended for joint review. The primary hypothesis being tested in this trial is that Org 10172 in conjunction to conventional medical care is superior to the combination of conventional medical care and placebo in improving the likelihood of a favorable outcome at three months after stroke. Antithrombotic drugs have been used in the early management of patients with acute ischemic stroke for more than 50 years. The drugs were given to prevent recurrent embolism, progression of a thrombosis, or failure of collateral circulation. These drugs may also be an important adjunct to thrombolytic therapy. Despite their widespread use, there is still considerable controversy about their efficacy and safety. The controversy largely results from the absence of any data that support the indications or contraindications for these drugs. Heparin has been complicated by serious hemorrhagic side effects and thrombocytopenia. Low molecular weight antithrombotic drugs such as Org 10172 may be safer than conventional heparin. Org 10172 is being used to prevent venous thromboses and to treat heparin-induced thrombocytopenia. Pilot studies of Org 10172 in patients with acute ischemic stroke were promising and these data were used to develop the trial that is currently underway. This carefully designed and conducted trial was funded in January, 1990. To date, the investigators have enrolled more than 650 patients of the planned 1300 at the 26 participating centers. The trial has been successful in recruiting women and minorities as subjects in this trial. A number of publications from the trial have already appeared. These papers report our development and testing of methods to conduct the trial and some baseline data. The trial recently had its mid-study interim analysis and our NINDS Safety and Monitoring Committee authorized our continued recruitment and treatment of patients. At the time of our interim analysis more than 99% of expected data had been entered in our data system. Although we are behind in recruitment, partially as the result of prolonged regulatory and administrative delays, we can achieve our goal to complete this trial. We are requesting approval and continued funding to complete this important trial. It is unlikely that future trials, of this size and scope, will test antithrombotic therapy in acute stroke.