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Post-Injury Platelet Biology: Mechanisms and Outcomes

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ClinicalTrials.gov Identifier: NCT03682757
Recruitment Status : Recruiting
First Posted : September 25, 2018
Last Update Posted : August 20, 2020
Sponsor:
Collaborators:
University of Colorado, Denver
University of Utah
University of California, Berkeley
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Trauma-induced coagulopathy is a central cause of preventable deaths from hemorrhage after injury. The contribution and impact of altered post injury platelet biology on trauma-induced coagulopathy is not well understood despite the pivotal contribution of platelets to normal coagulation and endothelial integrity. The central hypothesis for this study is that severe injury and shock drive altered platelet activation, platelet aggregation, and platelet-endothelial interactions that are associated with increased rates of transfusion, organ failure, and mortality. This study will investigate these causal pathways, mechanisms, and associated outcomes in a prospective observational trauma cohort through collection of biospecimens and detailed clinical data.

Condition or disease
Wound and Injuries Blood Platelets Endothelium

Detailed Description:
This is a prospective cohort study of trauma patients on admission to the emergency department and for the subsequent 28 days. All adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital and Trauma center, a level-1 trauma center, are eligible for enrollment. A 20-ml sample of blood will be drawn within 10 minutes of arrival in the emergency department (ED), processed in the central laboratory, and plasma stored at -80°C. Blood samples will be collected immediately on presentation via initial placement of a 16-gauge or larger peripheral intravenous line. Plasma biomarkers of endothelial injury will be measured by enzyme-linked immunosorbent assays (von Willebrand factor, syndecan-1, and angiopoietin-2). Cellular biomarkers of platelet activation will be measured by flow cytometry (platelet-monocyte aggregates, integrin αIIbβ3, P-selectin, and platelet microparticles). Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry. The effect of post-injury platelets on endothelial integrity will be quantified by in vitro assays of platelet-induced endothelial permeability. Comprehensive demographic data and medical history will be collected from chart review, interviews of patients and family members. Detailed clinical and outcome data is collected including transfusion timing and doses, the incidence of organ failure (Denver Postinjury Multiple Organ Failure Score), acute respiratory distress syndrome (Berlin Definition), infection, symptomatic thromboembolic complications, ventilator-free days, length of intensive care unit (ICU) and hospital stay, and mortality (6 hours, 24 hours, 30 days). In hospital mortality after 30 days will be assessed for all patients. Standard coagulation measures (international normalized ratio, prothrombin time, platelet count) and other laboratory measures will be collected to account and control for other distinct but highly integrated pathways implicated in trauma-induced coagulopathy. The Trauma Registry, a large database managed under guidelines from the American Trauma society, uses chart review to retrospectively assign Injury Severity Scores (ISS) and Abbreviated Injury Scores (AIS).

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Post-Injury Platelet Biology: Mechanisms and Outcomes
Actual Study Start Date : September 20, 2018
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Group/Cohort
Severe Injury/Shock
Severely injured trauma patients presenting with shock, as defined by an Injury Severity Score (ISS)>=25, and base deficit (BD)>=6.
Without Severe Injury/Shock
Not severely injured trauma patients presenting without shock, as defined by an Injury Severity Score (ISS)<25, and base deficit (BD) <6.
Healthy Controls
Uninjured healthy volunteers



Primary Outcome Measures :
  1. In Vitro Measurement of Endothelial Biomarkers [ Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department) ]
    Plasma biomarkers of endothelial injury will be measured by enzyme-linked immunosorbent assays (von Willebrand factor, syndecan-1, and angiopoietin-2).

  2. In Vitro Measurement Platelet Activation Biomarkers [ Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department) ]
    Cellular biomarkers of platelet activation will be measured by flow cytometry (platelet-monocyte aggregates, integrin αIIbβ3, P-selectin, and platelet microparticles).

  3. In Vitro Measurement of Platelet Aggregation [ Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department) ]
    Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry.

  4. In Vitro Assays of Platelet-Induced Endothelial Permeability [ Time Frame: 0 hour (within 10 minutes of arrival to the Emergency Department) ]
    The effect of post-injury platelets on endothelial integrity will be quantified by in vitro assays of platelet-induced endothelial permeability using transendothelial permeability electrical resistance (TEER) assays.

  5. Transfusion products received (red cell, plasma, platelet) [ Time Frame: in first 24 hours after arrival to the emergency department ]
    Continuous units of red cell, plasma, platelet; transfused in 24 hours (yes/no); massive transfusion (>10units red cell/24 hour, yes/no)

  6. Organ Failure [ Time Frame: Within 1 week of arrival to the emergency department ]
    Rates of organ failure (yes/no) (Denver Postinjury Multiple Organ Failure Score)

  7. 6-hour Mortality [ Time Frame: 6 hours after arrival to the emergency department ]
  8. 24-hour Mortality [ Time Frame: 24 hours after arrival to the emergency department ]
  9. 30-days Mortality [ Time Frame: 30 days after arrival to the emergency department ]
  10. Hospital Discharge Mortality [ Time Frame: Through hospital discharge (an average of 13 days) ]

Biospecimen Retention:   Samples Without DNA
Whole blood, plasma


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital
Criteria

Inclusion Criteria:

  • Adult patients meeting criteria for full trauma team activation and admitted to Zuckerberg San Francisco General Hospital.

Exclusion Criteria:

  • Patients <18 years old
  • Patients transferred from other hospitals
  • Patients who are pregnant
  • Patients who are incarcerated
  • Patients will be retrospectively excluded if they were taking anticoagulant or anti-platelet medications, have moderate or severe liver disease, or a known bleeding diathesis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03682757


Contacts
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Contact: Lucy Kornblith, MD 415-206-6946 Lucy.Kornblith@ucsf.edu

Locations
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United States, California
Zuckerberg San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Lucy Kornblith, MD    415-206-6946    Lucy.Kornblith@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
University of Colorado, Denver
University of Utah
University of California, Berkeley
Investigators
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Principal Investigator: Lucy Kornblith, MD University of California, San Francisco
Publications:

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03682757    
Other Study ID Numbers: P0528296
First Posted: September 25, 2018    Key Record Dates
Last Update Posted: August 20, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of California, San Francisco:
Trauma
Platelets
Coagulopathy
Additional relevant MeSH terms:
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Wounds and Injuries