Type: RandomisedRandomised means that patients accepted into the study are randomly allocated to receive one or other of the alternative treatments., double-blindedA double-blinded trial means that neither the patient nor the researchers know whether any given individual has received which of the different treatments until after the data has been collected and analysed., placebo-controlledA placebo is a drug designed to have no real effect on the patient. A placebo-controlled study means that some patients will receive the drug being tested and other patients receive a placebo. This enables researchers to compare how patients respond to the drug and the placebo. .
Phase: Phase 3Phase 3 trials compare new treatments with the best currently available treatment (the standard treatment). Phase 3 is sometimes written as phase III. Phase 3 trials usually involve many more patients than phase 1 or 2. This is because differences in success rates may be small, so the trial needs many patients to be able to show the difference.
Size: Multicentre, international
Current status: Open
Recruitment to date: 185
The CRASH-3 trial is sponsored by the London School of Hygiene & Tropical Medicine (LSHTM), and is led nationally by the Chief Investigator, Professor Ian Roberts.
This study is designed to test the use of a drug called tranexamic acid (TXA) for the treatment of significant traumatic brain injury.
TXA is a type of drug known as a fibrinolytic agent, which means it inhibits the body’s ability to break down a substance called fibrin. Fibrin plays a key role in blood clotting, so preventing its breakdown helps the body to stop bleeding.
TXA is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. A systematic review of randomised trials of TXA in elective surgical patients shows that TXA reduces the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding.
More recently, TXA has been shown to reduce death rates in trauma patients with significant bleeding. The CRASH-2 trial, which enrolled 20,211 bleeding trauma patients from hospitals in 40 countries, showed that the administration of TXA within 8 hours of injury significantly reduces deaths due to bleeding without any serious complications.
Among patients treated very soon after injury, the reduction in mortality with TXA is even greater.
The knowledge that TXA reduces blood loss in surgery and reduces mortality in traumatic bleeding raises the possibility that it might also be effective in treating patients who have a traumatic brain injury. Two studies have shown promising results but CRASH-3 seeks to provide conclusive evidence as to the effectiveness and safety of using TXA in patients with traumatic brain injury.
Who is eligible?
Patients are eligible to take part in this trial if they have suffered a traumatic brain injury and:
- can receive TXA within eight hours of injury
- have any intracranial bleeding on CT scan or who have a Glasgow Coma Score of 12 or less, and
- who have no significant extra cranial bleeding (needing immediate blood transfusion)
Once a patient has been identified as having a traumatic brain injury they will be assessed by medical staff for inclusion in the trial. It is important that the time of injury is known, as CRASH-3 is testing the use of TXA within eight hours of the injury.
Because most patients with traumatic brain injury are unable to consent to taking part in a trial, consent will be sought from a family member. If no family member is available, a process can be used to obtain approval from a senior doctor who is not connected with the trial. This ensures that patients who cannot consent themselves and do not have a family member available are still entitled to the same level of access to this trial as any other patient.
The patient is randomised to receive either TXA or a placebo. Neither the patient nor the clinicians knows whether the drug or the placebo has been prescribed. After receiving the initial dose over 10 minutes, the patient will then receive as second dose over eight hours.
Patients’ progress will be monitored at set points after their treatment, with the first tests conducted after 28 days. The serious nature of traumatic brain injury means that some patients do not survive their injuries, but their participation in the trial still provides valuable information which will help save and improve lives around the world.