Cold Stored Platelet in Hemorrhagic Shock (CriSP-HS)

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

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Trauma
• Intervention / Treatment: Biological: Cold Stored Platelets (CSP); Biological: Standard Care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jason Sperry, MD, MPH; Phone Number: 412 802 8270; Email: sperryjl@upmc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • San Francisco, California, United States, 94110
      • University of California San Francisco
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients with traumatic injury who meet the following criteria:

1. Has 2 or more of any of the following:

   1. Hypotension (systolic blood pressure ≤ 90 mmHg) in the prehospital or emergency department setting
   2. Penetrating mechanism
   3. 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
   4. Heart rate ≥ 120 in the prehospital or emergency department setting

   AND

2. 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:

1. Wearing "NO CriSP" opt-out bracelet
2. Age >90 or <15 years of age
3. Isolated fall from standing injury mechanism
4. Prisoner
5. Pregnant
6. Traumatic arrest with >5 minutes of CPR without return of vital signs
7. Brain matter exposed or penetrating brain injury (gun shot wound [GSW])
8. Isolated drowning or hanging victims
9. Isolated burns > estimated 20% total body surface area
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

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 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

Collaborators and Investigators

• Sponsor: Jason Sperry
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Jason Sperry, MD, MPH, University of Pittsburgh; Principal Investigator: Frank Guyette, MD, MPH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Actual): October 7, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: trauma; platelet; hemorrhagic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Hemorrhage; Shock, Hemorrhagic
• Other Study ID Numbers: STUDY21100002; W81XWH-16-D-0024 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator.
• IPD Sharing Time Frame: Data will become available after publication of the primary manuscript.
• IPD Sharing Access Criteria: Requests for data will be submitted in writing and reviewed by the Principal Investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No