Early Use of Cryoprecipitate With Major Hemorrhage Protocol (MHP) Activation

Study Overview
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Brief Summary
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The purpose of this trial is to compare standard of care (SOC) massive transfusion protocol to SOC massive transfusion protocol plus early use of cryoprecipitate (within 90 minutes of emergency department arrival).

Official Title
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A Multi-center, Randomized, Controlled Trial Evaluating the Effects of Early High-Dose Cryoprecipitate in Adult Patients With Major Trauma Hemorrhage Requiring Major Hemorrhage Protocol (MHP) Activation

Conditions
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Trauma Injury

Intervention / Treatment
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* Biological: Cryoprecipitate
* Biological: Red Blood Cells
* Biological: Plasma
* Biological: Platelets
* Biological: Whole Blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is judged to be an adult (according to local practice, e.g. 16 years or older in UK) and has sustained severe traumatic injury. In the event the age is unknown, estimated body weight ≥50 kg. The patient is deemed by the attending clinician to have on-going active hemorrhage AND REQUIRES Activation of the local major hemorrhage protocol for management of severe blood loss AND HAS STARTED or HAS RECEIVED at least one unit of any blood component Exclusion Criteria: The patient has been transferred from another hospital The trauma team leader deems the injuries incompatible with life More than 3 hours have elapsed from the time of injury Prisoner (as defined as someone admitted from a correctional facility) Known Do Not Resuscitate orders Enrolled in a concurrent ongoing interventional, randomized clinical trial Patients who wear opt out bracelet for study Obvious pregnancy Severely burned

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Cryoprecipitate + Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood)<br>Cryoprecipitate will be given in addition to the standard of care massive transfusion protocol products, which include red blood cells, plasma, platelets and whole blood. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units). | Biological: Cryoprecipitate<br>* Cryoprecipitate is a blood product high in fibrinogen. The Cryoprecipitate will be given with 90 minutes of emergency department arrival. Cryoprecipitate dose will be 3 pools (equivalent to 15 single units).<br>Biological: Red Blood Cells<br>* RBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>* Other names: RBCs;Biological: Plasma<br>* Plasma is utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>Biological: Platelets<br>* Platelets are utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>Biological: Whole Blood<br>* Whole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>|
| Active Comparator: Massive Transfusion Protocol (RBCs, Plasma, Platelets, Whole Blood)<br>Only standard of care massive transfusion protocol products will be given, including red blood cells, plasma, platelets, and whole blood. | Biological: Red Blood Cells<br>* RBCs are utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>* Other names: RBCs;Biological: Plasma<br>* Plasma is utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>Biological: Platelets<br>* Platelets are utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>Biological: Whole Blood<br>* Whole Blood is utilized as part of the Massive Transfusion protocol for hemorrhage control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Mortality From Any Cause | Mortality from any cause | 28 days after emergency department (ED) admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Mortality at 6 Hours | Mortality from any cause | 6 hours after ED admission | 
| All Cause Mortality at 24 Hours | Mortality from any cause | 24 hours after ED admission | 
| All Cause Mortality at 6 Months | Mortality from any cause | 6 months after ED admission | 
| All Cause Mortality at 12 Months | Mortality from any cause | 12 months after ED admission | 
| Death From Bleeding at 6 Hours | Death related to exsanguination | 6 hours after ED admission | 
| Death From Bleeding at 24 Hours | Death related to exsanguination | 24 hours after ED admission | 
| Transfusion Requirements (Number of Units of Red Blood Cells (RBCs)) | Number of units of RBCs | from time of pre-hospital care to 24 hours after ED admission | 
| Transfusion Requirements (Number of Units of Plasma) | Number of units of plasma | from time of pre-hospital care to 24 hours after ED admission | 
| Transfusion Requirements (Number of Units of Platelets) | Number of units of platelets | from time of pre-hospital care to 24 hours after ED admission | 
| Transfusion Requirements (Number of Units of Cryoprecipitate) | Number of units of cryoprecipitate | from time of pre-hospital care to 24 hours after ED admission | 
| Destination of Participant at Time of Discharge From Hospital | Disposition of subject at time of discharge | at the time of discharge from hospital, about 1-8 days after admission | 
| Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L) | EQ5D-5L is reported as an index score ranging from 0 to 1, where 0 is the health state equivalent to dead and 1 is the health state equivalent to full health. | Day of hospital discharge or 28 days after ED admission (whichever comes first) | 
| Quality of Life as Assessed by the Glasgow Outcome Score | The Glasgow Outcome Score ranges from 1 to 5, with a higher score indicating a better outcome: Death - Severe injury or death without recovery of consciousness Persistent vegetative state - Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions Severe disability - Severe injury with permanent need for help with daily living Moderate disability - No need for assistance in everyday life, employment is possible but may require special equipment Low disability - Light damage with minor neurological and psychological deficits | Day of hospital discharge or 28 days after ED admission (whichever comes first) | 
| Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ5D-5L) | EQ5D-5L is reported as an index score ranging from 0 to 1, where 0 is the health state equivalent to dead and 1 is the health state equivalent to full health. | 6 months after ED admission | 
| Quality of Life as Assessed by the Glasgow Outcome Score | The Glasgow Outcome Score ranges from 1 to 5, with a higher score indicating a better outcome: Death - Severe injury or death without recovery of consciousness Persistent vegetative state - Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions Severe disability - Severe injury with permanent need for help with daily living Moderate disability - No need for assistance in everyday life, employment is possible but may require special equipment Low disability - Light damage with minor neurological and psychological deficits | 6 months after ED admission | 
| Hospital Resource Use as Assessed by Number of Ventilator Days | Number of ventilator days during hospitalization | Day of hospital discharge or 28 days after ED admission (whichever comes first) | 
| Hospital Resource Use as Assessed by Number of Intensive Care Unit (ICU) Days | Number of ICU days during hospitalization | Day of hospital discharge or 28 days after ED admission (whichever comes first) | 
| Hospital Resource Use as Assessed by Number of Hospital Days | Total number of hospital days | Day of hospital discharge or 28 days after ED admission (whichever comes first) |