Cold Stored Platelet in Hemorrhagic Shock

Study Overview
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Brief Summary
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The Cold Stored Platelet Early Intervention in Hemorrhagic Shock (CriSP-HS) trial is a proposed 3 year, open label, multi-center, randomized trial designed to determine the feasibility, efficacy, and safety of urgent release cold stored platelets (CSP) in patients in hemorrhagic shock. Patients will be randomized to receive either standard care or early infusion of urgent release cold stored platelets (CSP). The proposed pilot study will utilize 5 level-1 trauma centers from within the LITES network and will enroll approximately 200 patients. The primary outcome for the pilot trial is feasibility, with principal secondary clinical outcome of 24 hour mortality.

Detailed Description
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The acute management of the severely injured patient with hemorrhage following trauma center arrival has evolved over the last decade. Current treatment priorities include prevention of coagulopathy through minimization of crystalloid and early blood component resuscitation including plasma and platelets in equal ratios with packed red blood cells. These in-hospital practices, termed damage control resuscitation, are widely used in both battlefield and civilian resuscitation following traumatic injury. Initiation of the tenets of damage control resuscitation early, soon after arrival, has the potential to reduce downstream complications attributable to hemorrhage by intervening closer to the time of injury, prior to the development of coagulopathy; irreversible shock; and the ensuing inflammatory response. Other blood constituents have recently been shown to be beneficial when given early. Thawed plasma transfusion has been shown to safely reduce 30-day mortality when infused early, in the prehospital setting, in patients at risk of hemorrhagic shock and this separation of survival occurs within the first 3 hours. Platelet transfusion is associated with improved outcomes in the acutely bleeding patients. Cold Stored Platelets have been reported to reduce blood loss when provided for hemorrhage and are a more effective hemostatic product. Cold stored platelets are less likely to become bacterial contaminated and were the standard of care platelet product until the 1980s. Despite this history and potential benefits, the risks associated with urgent release cold stored platelets and their respective efficacy and function over time are not known in patients with hemorrhagic shock. By providing Cold Stored Platelets in an urgent release fashion following injury, a potentially superior hemostatic agent is given early, closer to the time of injury. The current pilot trial was designed to determine the feasibility, efficacy and safety of urgent release cold stored platelets as compared to standard care in injured patients in hemorrhagic shock. There are no high-level data which appropriately characterize the urgent release use of cold stored platelets out to 14 days or their function over that time period as compared to standard room temperature platelets. These results will be able to inform future large randomized clinical trials allowing the most appropriate injured population, inclusion criteria, and primary outcome to be selected and utilized.

Official Title
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Cold Stored Platelet Early Intervention in Hemorrhagic Shock (CriSP-HS) Trial

Conditions
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Trauma, Hemorrhage

Intervention / Treatment
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* Biological: Cold Stored Platelets (CSP)
* Biological: Standard Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with traumatic injury who meet the following criteria: Has 2 or more of any of the following: Hypotension (systolic blood pressure ≤ 90 mmHg) in the prehospital or emergency department setting Penetrating mechanism Abdominal or Extended Focused Assessment with Sonography for Trauma (FAST) abdominal ultrasound is positive or equivocal or deferred by clinical team due to emergent visit to Interventional Radiology or a need for emergent laparotomy, thoracotomy, or vascular exploration Heart rate ≥ 120 in the prehospital or emergency department setting AND Clinical team deems Operating Room (laparotomy, thoracotomy or vascular exploration) or Interventional Radiology for embolization within 60 minutes of arrival to be clinically indicated. Exclusion Criteria: Wearing NO CriSP opt-out bracelet Age >90 or <15 years of age Isolated fall from standing injury mechanism Prisoner Pregnant Traumatic arrest with >5 minutes of CPR without return of vital signs Brain matter exposed or penetrating brain injury (gun shot wound [GSW]) Isolated drowning or hanging victims Isolated burns > estimated 20% total body surface area Objection to study voiced by subject or family member in Emergency Department Inclusion and exclusion criteria will be assessed based on information available at the time of enrollment. If, after subsequent review, it is determined that the subject did not meet inclusion criteria and/or met exclusion criteria, the subject will remain enrolled in the study based on the intent-to-treat principle. If a verbal report must be used in lieu of physical documentation or directly witnessing inclusion criteria, documentation of the verbal report will serve as the source documentation for determining eligibility.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 90 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
Interventional Model Description: permuted block design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cold-stored Platelet (CSP)<br>early infusion of one apheresis unit urgent release cold stored platelets (CSP) | Biological: Cold Stored Platelets (CSP)<br>* early infusion of urgent release CSP<br>|
| Active Comparator: Standard Care<br>resuscitation, blood and blood component transfusion per site standard care | Biological: Standard Care<br>* standard care including blood and blood component therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study feasibility | proportion of eligible patients that can be randomized, enrolled, adhere to protocol, and complete follow-up | Enrollment through 30 days or discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour mortality | Mortality within 24 hours | Enrollment through 24 hours | 
| 3-hour mortality | Mortality within 3 hours | Enrollment through 3 hours | 
| In hospital mortality | mortality in-hospital | Enrollment through 30 days or discharge | 
| Death from hemorrhage | mortality due to hemorrhage | Enrollment through 24 hours | 
| Blood or blood component type required for transfusion | Type of blood and/or blood components required to be transfused | Enrollment through 24 hours | 
| Amount of blood or blood component required for transfusion | number of units of blood and/or blood components required to be transfused | Enrollment through 24 hours | 
| Incidence of acute respiratory distress syndrome (ARDS) | Berlin definition of mild ARDS will determine incidence and will be further stratified into Moderate and Severe | Enrollment through 48 hours | 
| Time to hemostasis | Amount of time from randomization to point of nadir transfusion requirement of 1 unit of red blood cells in a 60-minute time period | Enrollment through 4 hours | 
| Incidence of coagulopathy by rapid thrombelastography (rTEG) | Coagulopathy as indicated by rTEG measures | Enrollment through 48 hours | 
| Incidence of allergic/transfusion reaction | Any transfusion complication in Emergency Department or Operating Room/Interventional Radiology | Enrollment through 24 hours | 
| Incidence of transfusion related acute lung injury (TRALI) | Occurrence of ARDS within 6 hours of transfusion of blood product | Enrollment through 48 hours | 
| rTEG measurement of platelet hemostatic function | rTEG | 60 minutes and 24 hours after arrival | 
| Prothrombin Time (PT) measurement of platelet hemostatic function | PT | 60 minutes and 24 hours after arrival | 
| International Normalized Ratio (INR) measurement of platelet hemostatic function | INR | 60 minutes and 24 hours after arrival | 
| Incidence of thromboembolic events | Incidence of pulmonary embolism, venous thrombosis, or arterial thrombosis | Enrollment through 48 hours | 
| 30-day mortality | mortality within 30 days | Enrollment through 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet, hemorrhagic shock, trauma