The CRASH-3 Trial: Tranexamic acid for the treatment of significant traumatic brain injury.

CRASH-3 试验：氨甲环酸用于治疗严重的创伤性脑损伤。

• 批准号: MR/M009211/1
• 负责人: Ian Roberts
• 金额: $ 362.02万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM009211%2F1
• 关键词: CRASH; Trial; Tranexamic; acid; treatment

There are more deaths each year from injuries than from HIV, TB and malaria combined. Worldwide, about ten million people are killed or hospitalised because of a head injury every year. Most head injuries are caused by road traffic crashes, and because car use is increasing, the number of people suffering a head injury is increasing. Amongst those who survive a head injury, many are left severely disabled for the rest of their lives. For example, there is a high likelihood that Michael Schumacher will be permanently disabled as a result of his recent head injury. Most victims of head injury are young adults living in low and middle income countries. Because many of the victims are also breadwinners for their families, head injuries can also result in loss of income which, along with medical costs, can increase household debt and lead to a fall in living standards for the whole family. When the head is injured there is often bleeding inside the brain, which can continue for some time and worsen after hospital admission. This bleeding increases pressure inside the skull causing further damage to the brain, which can be fatal or result in serious disability for the patient. We think that we can prevent some of these deaths and disability by reducing the amount of bleeding in the brain after head injury. Tranexamic acid is a cheap drug that reduces bleeding in other conditions. A large trial in accident victims (other than those with head injury) found that it reduces the chances of bleeding to death. If this drug also works in patients with head injury and bleeding into the brain, this would be important to know because it could save lives at a very low cost.We have already done two preparatory studies to see if tranexamic acid can help people who have bleeding inside the brain because of a head injury. Together, the results of the studies suggest that tranexamic acid should reduce the amount of bleeding inside the brain and could reduce their chances of dying or being disabled. However, because these studies were small, we are not very certain about the accuracy of their results. Also, they were not designed to find out whether tranexamic acid reduces disability. Because doctors are still unsure about whether tranexamic acid works, it is not given to patients with traumatic brain injury. But if a new clinical trial showed that it worked, this would change very quickly. We want to find out if tranexamic acid saves lives and reduces disability in people with traumatic brain injury.We plan to study 10,000 patients with traumatic brain injury in countries throughout the world. We will give half of them tranexamic acid and the other half a dummy medicine called a placebo. To make sure that the two groups are the same apart from tranexamic acid, we will decide who gets tranexamic acid and who gets placebo using the modern equivalent of the toss of a coin (this is called randomisation). Everyone will of course get all the treatments that doctors usually give to traumatically brain injured patients. At the end of the trial we will see if giving tranexamic acid on top of all the usual treatments improves survival and other patient outcomes. The study will be carried out by a team of researchers with lots of experience in doing clinical trials. In fact, it will be the same team that did the successful study of tranexamic acid in accident victims. The trial will cost several million pounds but if it shows (as we hope it will) that tranexamic acid works, we will have a very cheap way of reducing the number of people who die and are disabled after a head injury. The start up phase of trial is underway and over a thousand patients have been recruited. The trial procedures work well. This application is for funds to continue recruitment to 10,000 patients.

每年因受伤而死亡的人数超过艾滋病毒、结核病和疟疾的总和。全世界每年约有1000万人因头部受伤而死亡或住院。大多数头部受伤是由道路交通事故造成的，由于汽车使用的增加，头部受伤的人数也在增加。在那些头部受伤的幸存者中，许多人在余生中严重残疾。例如，迈克尔·舒马赫很有可能因最近的头部受伤而永久残疾。大多数头部受伤的受害者是生活在低收入和中等收入国家的年轻人。由于许多受害者也是家庭的经济支柱，头部受伤也可能导致收入损失，这沿着医疗费用，可能增加家庭债务，导致全家生活水平下降。当头部受伤时，脑内通常会出血，这种情况可能会持续一段时间，并在入院后恶化。这种出血会增加颅骨内的压力，导致对大脑的进一步损伤，这可能是致命的或导致患者严重残疾。我们认为，我们可以通过减少头部受伤后大脑中的出血量来预防其中一些死亡和残疾。氨甲环酸是一种廉价的药物，可以减少其他情况下的出血。在事故受害者（头部受伤者除外）中进行的一项大型试验发现，它降低了出血致死的可能性。如果氨甲环酸对脑损伤和脑出血的患者也有效，这一点很重要，因为它可以以很低的成本挽救生命。我们已经做了两项预备性研究，看看氨甲环酸是否可以帮助因脑损伤而脑出血的人。总之，研究结果表明，氨甲环酸应该减少大脑内的出血量，并可以减少他们死亡或残疾的机会。然而，由于这些研究规模较小，我们对其结果的准确性不是很确定。此外，他们并不是为了找出氨甲环酸是否能减少残疾。因为医生们仍然不确定氨甲环酸是否有效，所以它不用于创伤性脑损伤患者。但是，如果一项新的临床试验表明它有效，这种情况将很快改变。我们想知道氨甲环酸是否能挽救创伤性脑损伤患者的生命，减少他们的残疾。我们计划对世界各国的1万名创伤性脑损伤患者进行研究。我们会给一半的人氨甲环酸，另一半人服用一种叫做安慰剂的假药。为了确保除了氨甲环酸之外，两组都是相同的，我们将使用相当于抛硬币的现代方法来决定谁服用氨甲环酸，谁服用安慰剂（这被称为随机化）。当然，每个人都会得到医生通常给予脑外伤患者的所有治疗。在试验结束时，我们将观察在所有常规治疗的基础上给予氨甲环酸是否能改善生存率和其他患者结局。这项研究将由一组具有丰富临床试验经验的研究人员进行。事实上，这将是成功研究事故受害者氨甲环酸的同一个团队。这项试验将花费数百万英镑，但如果它表明（正如我们所希望的那样）氨甲环酸有效，我们将有一个非常便宜的方法来减少头部受伤后死亡和残疾的人数。试验的启动阶段正在进行中，已招募了1000多名患者。审判程序运作良好。这份申请是为了继续招募10,000名患者。

项目成果

Additional file 8: of A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3...

附加文件 8：关于氨甲环酸与安慰剂对孤立性创伤性脑损伤中颅内出血和脑缺血影响的嵌套机制子研究：随机对照试验的研究方案（CRASH-3...

• DOI: 10.6084/m9.figshare.c.3829030_d8
• 发表时间: 2017
• 作者: Abda Mahmood

Additional file 1: of A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3...

附加文件 1：关于氨甲环酸与安慰剂对孤立性创伤性脑损伤中颅内出血和脑缺血影响的嵌套机制子研究：随机对照试验的研究方案（CRASH-3...

• DOI: 10.6084/m9.figshare.c.3829030_d1
• 发表时间: 2017
• 作者: Abda Mahmood

Additional file 4: of A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3...

附加文件 4：关于氨甲环酸与安慰剂对孤立性创伤性脑损伤中颅内出血和脑缺血影响的嵌套机制子研究：随机对照试验的研究方案（CRASH-3...

• DOI: 10.6084/m9.figshare.c.3829030_d4
• 发表时间: 2017
• 作者: Abda Mahmood

Additional file 6: of A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3...

附加文件 6：关于氨甲环酸与安慰剂对孤立性创伤性脑损伤中颅内出血和脑缺血影响的嵌套机制子研究：随机对照试验的研究方案（CRASH-3...

• DOI: 10.6084/m9.figshare.c.3829030_d6
• 发表时间: 2017
• 作者: Abda Mahmood

Additional file 3: of A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3...

附加文件 3：关于氨甲环酸与安慰剂对孤立性创伤性脑损伤中颅内出血和脑缺血影响的嵌套机制子研究：随机对照试验的研究方案（CRASH-3...

• DOI: 10.6084/m9.figshare.c.3829030_d3
• 发表时间: 2017
• 作者: Abda Mahmood