Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage

Study Overview
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Brief Summary
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CRASH 2 is a large pragmatic randomised placebo controlled trial of the effects of the early administration of the antifibrinolytic agent tranexamic acid on death, vascular events and transfusion requirements. Adults with trauma who are within 8 hours of injury and have either significant haemorrhage, or who are considered to be at risk of significant haemorrhage, are eligible if the responsible doctor is for any reason substantially uncertain whether or not to use an antifibrinolytic agent. Numbered drug or placebo packs will be available in each participating emergency department. Randomisation will involve calling a 24-hour freecall randomisation service. The call should last only a minute or two and at the end of it the randomisation service will specify which numbered treatment pack to use. For hospitals where telephone randomisation is not feasible, randomisation will be by taking the next consecutively numbered treatment pack. No extra tests are required but a short form must be completed one month later or on discharge or on death (whichever occurs first).

Detailed Description
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See trial website for full protocol. This is an international trial with over 300 hospitals in about 40 countries worldwide.

Official Title
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A Large Randomised Placebo Controlled Trial Among Trauma Patients With, or at Risk of, Significant Haemorrhage, of the Effects of Antifibrinolytic Treatment on Death and Transfusion Requirement

Conditions
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Hemorrhage

Intervention / Treatment
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* Drug: Tranexamic acid
* Drug: Sodium Chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All trauma patients with ongoing significant haemorrhage (systolic blood pressure less than 90 mmHg and/or heart rate more than 110 beats per minute), or who are considered to be at risk of significant haemorrhage, and are within 8 hours of the injury, are eligible for trial entry if they appear to be at least 16 years old. Although entry is allowed up to 8 hours from injury, the earlier that patients can be treated the better. Exclusion Criteria: The fundamental eligibility criterion is the responsible doctor's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular adult with traumatic haemorrhage. Patients for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised. Likewise, patients for whom there is considered to be a clear contraindication to antifibrinolytic therapy (such as, perhaps, those who have clinical evidence of a thrombotic disseminated intravascular coagulation) should not be randomised. Where the responsible doctor is substantially uncertain as to whether or not to use an antifibrinolytic, all these patients are eligible for randomisation and should be considered for the trial. There are no other pre-specified exclusion criteria

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Active | Drug: Tranexamic acid<br>* Loading dose of 1 gram then 1 gram by infusion over 8 hours<br>|
| Placebo Comparator: 2<br> | Drug: Sodium Chloride 0.9%<br>* Visual matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death in hospital within four weeks of injury (causes of death will be described to assess whether deaths were due to haemorrhage or vascular occlusion). |  | Death, discharge or four weeks post randomisation whichever occurs first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Receipt of a blood products transfusion, the number of units of blood products transfused, surgical intervention, and the occurrence of thrombo-embolic episodes |  | Death, discharge or four weeks post randomisation whichever occurs first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult trauma patients with ongoing significant haemorrhage or at risk of significant haemorrhage