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

每年死于伤害的人数比死于艾滋病毒、结核病和疟疾的总和还要多。在世界范围内，每年约有1000万人因头部受伤而死亡或住院。大多数头部损伤是由道路交通事故造成的，由于汽车使用量的增加，头部受伤的人数也在增加。在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·舒马赫很有可能会因为最近的头部受伤而永久残疾。大多数头部损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养家糊口者，头部受伤还可能导致收入损失，与医疗费用一起，可能会增加家庭债务，导致整个家庭的生活水平下降。当头部受伤时，大脑内部经常会出血，这种情况可能会持续一段时间，并在入院后恶化。这种出血会增加头骨内的压力，对大脑造成进一步的损害，这可能是致命的，或导致患者严重残疾。我们认为，通过减少头部损伤后脑内的出血量，我们可以预防其中一些死亡和残疾。氨甲环酸是一种廉价的药物，可以在其他情况下减少出血。在事故受害者(不包括头部受伤的人)中进行的一项大型试验发现，它可以降低失血致死的几率。如果这种药物对头部损伤和脑出血的患者也有效，那么了解这一点将是很重要的，因为它可以以非常低的成本拯救生命。我们已经做了两项预备研究，看看氨甲环酸是否可以帮助因头部损伤而出现脑内出血的人。总而言之，研究结果表明，氨甲环酸应该会减少大脑内的出血量，并可能降低他们死亡或残疾的机会。然而，由于这些研究的规模很小，我们不太确定他们结果的准确性。此外，他们的设计也不是为了找出氨甲环酸是否能减少残疾。由于医生仍不确定氨甲环酸是否有效，因此它不适用于创伤性脑损伤患者。但如果一项新的临床试验表明它有效，这种情况将很快改变。我们想要找出氨甲环酸是否能拯救创伤性脑损伤患者的生命并减少他们的残疾。我们计划对世界各国的10,000名创伤性脑损伤患者进行研究。我们将给其中一半人服用氨甲环酸，另一半人服用一种名为安慰剂的虚拟药物。为了确保除了氨甲环酸之外，这两组人的情况相同，我们将使用现代的掷硬币法(这称为随机化)来决定谁服用氨甲环酸，谁服用安慰剂。当然，每个人都将得到医生通常为脑外伤患者提供的所有治疗。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会改善患者的存活率和其他结果。这项研究将由一组在进行临床试验方面经验丰富的研究人员进行。事实上，成功研究氨甲环酸在事故受害者身上的团队将是同一个团队。这项试验将耗资数百万英镑，但如果它表明(正如我们希望的那样)氨甲环酸有效，我们将有一个非常廉价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。这项申请是为了获得继续招募10,000名患者的资金。

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.