Traumatic Brain Injury
Conditions
Keywords
Traumatic Brain Injury, Cold Stored Platelets
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.
Interventions
BIOLOGICALCold Stored Platelets
early infusion of urgent release CSP
BIOLOGICALStandard Care
standard care including room temperature platelets
Sponsors
United States Department of Defense
Jason Sperry
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
permuted block design
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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: 1. History or indication of pre-injury antiplatelet agent use 2. Need for platelet transfusion per standard practice
Exclusion criteria
1. Wearing NO CriSP opt out bracelet 2. Hypotension in Emergency Department (SBP\< 90 mmHg) 3. Age \> 89 or \< 18 years of age 4. Penetrating injury 5. Prisoner 6. Pregnancy 7. Going to operating room for non-neurosurgical intervention in first 60 minutes 8. Platelet transfusion contraindications per care team (for example, recent vascular stent, embolic stroke, intracranial and/or vascular lesions) 9. Objection to study voiced by participant or family member in Emergency Department 10. Currently on therapeutic anticoagulant in addition to aspirin and/or clopidogrel (e.g. warfarin, direct-acting oral anticoagulants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Feasibility | 6 months | proportion of eligible patients that can be randomized, enrolled, adhere to protocol, and complete follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Mortality | Enrollment through 24 hours | Mortality within 24 hours |
| In-hospital Mortality | Enrollment through discharge up to 6 months | Mortality in-hospital |
| TBI Progression | Enrollment through 24 hours | Evidence of progression of TBI. Common Data Elements for CT scan indicators of TBI progression will be utilized. |
| 6-month Extended Glasgow Outcome Scale (GOS-E) | 6 months after enrollment | 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). |
| Incidence of Allergic/Transfusion Reaction | Enrollment through 24 hours | Any transfusion complication in Emergency Department or Operating Room |
| Incidence of Transfusion Related Acute Lung Injury (TRALI) | Enrollment through 48 hours | Occurrence of Acute Respiratory Distress Syndrome (ARDS) within 6 hours of transfusion of platelets |
| Incidence of Thromboembolic Events | Enrollment through 48 hours | Incidence of pulmonary embolism, venous thrombosis, or arterial thrombosis |
| Galveston Orientation and Amnesia Test (GOAT) | At Discharge from Current Hospital Admission | 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.Range is 0-100. A score of 66 or lower is categorized as impaired, 66-75 as borderline, and 76-100 as normal. This will be obtained At Discharge from Current Hospital Admission |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cold-stored Platelet (CSP) early infusion of up to 2 units of urgent release cold stored platelets (CSP)
Cold Stored Platelets: early infusion of urgent release CSP | 50 |
| Standard Care standard care therapy
Standard Care: standard care including room temperature platelets | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Cold-stored Platelet (CSP) | Total | Standard Care |
|---|---|---|---|
| Age, Continuous | 73.5 years | 76 years | 78 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) White | 44 Participants | 81 Participants | 37 Participants |
| Region of Enrollment United States | 50 Participants | 100 Participants | 50 Participants |
| Sex: Female, Male Female | 23 Participants | 47 Participants | 24 Participants |
| Sex: Female, Male Male | 27 Participants | 53 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 50 | 7 / 49 |
| other Total, other adverse events | 0 / 50 | 0 / 49 |
| serious Total, serious adverse events | 9 / 50 | 8 / 49 |
Outcome results
Primary
Study Feasibility
proportion of eligible patients that can be randomized, enrolled, adhere to protocol, and complete follow-up
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | Study Feasibility | 50 Participants |
| Standard Care | Study Feasibility | 50 Participants |
Secondary
24-hour Mortality
Mortality within 24 hours
Time frame: Enrollment through 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | 24-hour Mortality | 1 Participants |
| Standard Care | 24-hour Mortality | 0 Participants |
Secondary
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).
Time frame: 6 months after enrollment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cold-stored Platelet (CSP) | 6-month Extended Glasgow Outcome Scale (GOS-E) | Unfavorable | 21 Participants |
| Cold-stored Platelet (CSP) | 6-month Extended Glasgow Outcome Scale (GOS-E) | Favorable | 22 Participants |
| Standard Care | 6-month Extended Glasgow Outcome Scale (GOS-E) | Unfavorable | 20 Participants |
| Standard Care | 6-month Extended Glasgow Outcome Scale (GOS-E) | Favorable | 20 Participants |
Secondary
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.Range is 0-100. A score of 66 or lower is categorized as impaired, 66-75 as borderline, and 76-100 as normal. This will be obtained At Discharge from Current Hospital Admission
Time frame: At Discharge from Current Hospital Admission
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cold-stored Platelet (CSP) | Galveston Orientation and Amnesia Test (GOAT) | 95 score on a scale |
| Standard Care | Galveston Orientation and Amnesia Test (GOAT) | 91 score on a scale |
Secondary
Incidence of Allergic/Transfusion Reaction
Any transfusion complication in Emergency Department or Operating Room
Time frame: Enrollment through 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | Incidence of Allergic/Transfusion Reaction | 0 Participants |
| Standard Care | Incidence of Allergic/Transfusion Reaction | 0 Participants |
Secondary
Incidence of Thromboembolic Events
Incidence of pulmonary embolism, venous thrombosis, or arterial thrombosis
Time frame: Enrollment through 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | Incidence of Thromboembolic Events | 1 Participants |
| Standard Care | Incidence of Thromboembolic Events | 0 Participants |
Secondary
Incidence of Transfusion Related Acute Lung Injury (TRALI)
Occurrence of Acute Respiratory Distress Syndrome (ARDS) within 6 hours of transfusion of platelets
Time frame: Enrollment through 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | Incidence of Transfusion Related Acute Lung Injury (TRALI) | 0 Participants |
| Standard Care | Incidence of Transfusion Related Acute Lung Injury (TRALI) | 0 Participants |
Secondary
In-hospital Mortality
Mortality in-hospital
Time frame: Enrollment through discharge up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | In-hospital Mortality | 6 Participants |
| Standard Care | In-hospital Mortality | 7 Participants |
Secondary
TBI Progression
Evidence of progression of TBI. Common Data Elements for CT scan indicators of TBI progression will be utilized.
Time frame: Enrollment through 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cold-stored Platelet (CSP) | TBI Progression | 8 Participants |
| Standard Care | TBI Progression | 11 Participants |