The IST-3 Co-ordinating Centre, Neurosciences Trial Unit, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Trials. 2011 Nov 30;12:252. doi: 10.1186/1745-6215-12-252.
Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.
International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.
The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.
The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.
ISRCTN25765518.
静脉注射重组组织型纤溶酶原激活物（rtPA）在欧洲被批准用于符合严格定义标准的急性缺血性脑卒中患者。IST-3 旨在提高急性缺血性脑卒中患者 rtPA 整体治疗效果（疗效和安全性）的外部有效性和精度，并确定更广泛的患者是否可能受益。
国际多中心前瞻性随机开放盲终点（PROBE）试验，评估急性缺血性脑卒中患者静脉注射 rtPA。适合的患者必须经过评估，并且能够在症状出现后 6 小时内开始治疗，并且脑影像学必须排除颅内出血和脑卒中模拟。
初始试验阶段为双盲，然后于 2003 年 8 月 1 日改为开放设计。招募于 2000 年 5 月 5 日开始，于 2011 年 7 月 31 日结束，共纳入 3035 例患者，其中只有 61 例（2%）符合 2003 年欧洲溶栓批准的标准。1617 例患者在试验入组时年龄超过 80 岁。分析计划将在不参考盲数据的情况下最终确定，并在 2012 年初试验数据未盲之前公布。主要试验结果将在 2012 年 5 月里斯本欧洲卒中会议上展示，旨在同时在同行评议期刊上发表。试验结果将在更新的 Cochrane 系统评价中呈现。我们还打算将试验数据纳入所有相关随机试验的个体患者数据荟萃分析中。
试验数据将：提高急性缺血性脑卒中患者静脉 rtPA 整体治疗效果（疗效和安全性）估计的外部有效性和精度；提供：关于不符合当前欧盟批准条件的不同类型患者静脉 rtPA 风险与获益平衡的新证据；并为 80 岁以上患者提供首个大规模随机证据，该年龄组在以前的急性脑卒中试验中基本被排除在外。
ISRCTN25765518。
