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、结核病和疟疾的人数加起来还要多。在世界范围内，每年约有1000万人因头部受伤而死亡或住院。大多数头部受伤是由道路交通事故造成的，而且由于汽车的使用在增加，头部受伤的人数也在增加。在那些头部受伤的幸存者中，许多人在他们的余生中都留下了严重的残疾。例如，迈克尔·舒马赫（Michael Schumacher）很有可能因为最近的头部受伤而终身残疾。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，加上医疗费用，可能增加家庭债务，导致整个家庭的生活水平下降。当头部受伤时，通常会出现脑内出血，这种情况会持续一段时间，住院后会恶化。这种出血增加了颅骨内的压力，导致大脑进一步受损，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的脑部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。一项针对事故受害者（不包括头部受伤的受害者）的大型试验发现，它可以降低因出血而死亡的几率。如果这种药物也适用于头部受伤和脑出血的患者，这将是很重要的，因为它可以以非常低的成本挽救生命。我们已经做了两项预备研究，看看氨甲环酸是否能帮助因头部受伤而颅内出血的人。综上所述，研究结果表明氨甲环酸可以减少脑内的出血量，从而降低患者死亡或致残的几率。然而，由于这些研究规模很小，我们不太确定其结果的准确性。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，所以它不被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。我们想知道氨甲环酸是否能挽救生命，减少创伤性脑损伤患者的残疾。我们计划在世界各国研究1万名创伤性脑损伤患者。我们会给一半的人服用氨甲环酸另一半的人服用安慰剂。为了确保两组人除了氨甲环酸之外都是一样的，我们将用现代的掷硬币的方式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创伤性脑损伤患者的所有治疗。在试验结束时，我们将看到在所有常规治疗之上给予氨甲环酸是否能提高生存率和其他患者预后。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体内氨甲环酸的同一团队。这项试验将花费数百万英镑，但如果它显示（正如我们所希望的那样）氨甲环酸起作用，我们将有一种非常廉价的方法来减少因头部受伤而死亡和致残的人数。试验的启动阶段正在进行中，已经招募了一千多名患者。审判程序运行良好。这个申请是为了继续招募10000名患者。

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.