Cold-stored Platelet Early Intervention in TBI

Study Overview
=================
Brief Summary
-----------------
The Cold Stored Platelet Early Intervention in Traumatic Brain Injury (CriSP-TBI) trial is a proposed 3 year, open label, single center, randomized trial designed to determine the feasibility, efficacy, and safety of urgent release cold stored platelets (CSP) in patients with TBI requiring platelet transfusion. Patients will be randomized to receive either standard care or early infusion of urgent release cold stored platelets (CSP). The proposed pilot study will enroll at the University of Pittsburgh and will enroll approximately 100 patients. The primary outcome for the pilot trial is feasibility, with principal secondary clinical outcome of 6-month Extended Glasgow Outcome Scale (GOS-E).

Detailed Description
-----------------
Platelet transfusion is commonly provided to patients with moderate or severe TBI who are on antiplatelet medications. Evidence suggests that patients on antiplatelet medications may have worse outcomes following TBI. Current literature has not demonstrated major outcome improvements in those patients who receive platelet transfusion. This lack of significant benefit may be due to insufficient dosing or due to the poor hemostatic function of standard care room temperature platelets. Studying the potential benefits of Cold Stored Platelet transfusion in the TBI population will provide needed direct comparison of room temperature and cold stored platelet transfusion which is unable to occur in patients with hemorrhagic shock, who may require large volumes of red blood cells and plasma concomitantly with platelet transfusion. 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 TBI patients requiring platelet transfusion. 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
-----------------
Cold Stored Platelet Early Intervention in Traumatic Brain Injury Trial

Conditions
-----------------
Traumatic Brain Injury

Intervention / Treatment
-----------------
* Biological: Cold Stored Platelets
* Biological: Standard Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with traumatic brain injury, defined by presence of potential progressive intracranial injury on CT scan, at significant risk for urgent neurosurgical procedure as determined by neurosurgical evaluation, who meet at least one of the following: History or indication of pre-injury antiplatelet agent use Need for platelet transfusion per standard practice Exclusion Criteria: Wearing NO CriSP opt out bracelet Hypotension in Emergency Department (SBP< 90 mmHg) Age > 89 or < 18 years of age Penetrating injury Prisoner Pregnancy Going to operating room for non-neurosurgical intervention in first 60 minutes Platelet transfusion contraindications per care team (for example, recent vascular stent, embolic stroke, intracranial and/or vascular lesions) Objection to study voiced by participant or family member in Emergency Department Currently on therapeutic anticoagulant in addition to aspirin and/or clopidogrel (e.g. warfarin, direct-acting oral anticoagulants)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 up to 2 units of urgent release cold stored platelets (CSP) | Biological: Cold Stored Platelets<br>* early infusion of urgent release CSP<br>|
| Active Comparator: Standard care<br>standard care therapy | Biological: Standard Care<br>* standard care including room temperature platelets<br>|

What is the study measuring?
-----------------
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 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Extended Glasgow Outcome Scale (GOS-E) | A tool used to characterize 6-month functional status into 8 defined categories, with 1 being the worst (death) to 8 being the most favorable (good recovery). | 6 months after enrollment | 
| 24-hour mortality | Mortality within 24 hours | Enrollment through 24 hours | 
| In-hospital mortality | Mortality in-hospital | Enrollment through discharge up to 6 months | 
| TBI Progression | Evidence of progression of TBI. Common Data Elements for CT scan indicators of TBI progression will be utilized. | Enrollment through 24 hours | 
| Galveston Orientation and Amnesia Test (GOAT) | 10-item questionnaire used to quickly assess post-traumatic amnesia following head injury. The GOAT is read orally to the patient and may be easily administered at the bedside. The total score accounts for orientation of person, place, and time, and recollection of events pre and post- injury. Cutoff scores are available to identify abnormal, borderline, and normal orientation. The total GOAT score is obtained by deducting the sum of the error points from each incorrect response from 100. A score of 66 or lower is categorized as impaired, 66-75 as borderline, and 76-100 as normal. | Enrollment through discharge up to 6 months | 
| Incidence of allergic/transfusion reaction | Any transfusion complication in Emergency Department or Operating Room | Enrollment through 24 hours | 
| Incidence of transfusion related acute lung injury (TRALI) | Occurrence of Acute Respiratory Distress Syndrome (ARDS) within 6 hours of transfusion of platelets | Enrollment through 48 hours | 
| rapid thrombelastography (rTEG) measurement of platelet hemostatic function | rTEG | Enrollment through 24 hours | 
| rTEG with platelet mapping | TEG-PM assessment of platelet function | Enrollment through 24 hours | 
| whole blood aggregometry test | test of platelet aggregation using low-dose collagen as a stimulus | Enrollment through 24 hours | 
| Incidence of thromboembolic events | Incidence of pulmonary embolism, venous thrombosis, or arterial thrombosis | Enrollment through 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Traumatic Brain Injury, Cold Stored Platelets