Post-Injury Platelet Biology: Mechanisms and Outcomes

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT03682757

Collaborator

University of Colorado, Denver (Other), University of Utah (Other), University of California, Berkeley (Other)

300

Enrollment

Location

59.4

Anticipated Duration (Months)

5.1

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Post-Injury Platelet Biology: Mechanisms and Outcomes

Actual Study Start Date :

Sep 20, 2018

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

In Vitro Measurement of Endothelial Biomarkers [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).
In Vitro Measurement Platelet Activation Biomarkers [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).
In Vitro Measurement of Platelet Aggregation [0 hour (within 10 minutes of arrival to the Emergency Department)]
Platelet aggregation will be measured by whole blood multiple electrode impedance aggregometry.
In Vitro Assays of Platelet-Induced Endothelial Permeability [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.
Transfusion products received (red cell, plasma, platelet) [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)
Organ Failure [Within 1 week of arrival to the emergency department]
Rates of organ failure (yes/no) (Denver Postinjury Multiple Organ Failure Score)
6-hour Mortality [6 hours after arrival to the emergency department]
24-hour Mortality [24 hours after arrival to the emergency department]
30-days Mortality [30 days after arrival to the emergency department]
Hospital Discharge Mortality [Through hospital discharge (an average of 13 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zuckerberg San Francisco General Hospital	San Francisco	California	United States	94110

Sponsors and Collaborators

University of California, San Francisco
University of Colorado, Denver
University of Utah
University of California, Berkeley

Investigators

Principal Investigator: Lucy Kornblith, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT03682757

Other Study ID Numbers:

P0528296

First Posted:

Sep 25, 2018

Last Update Posted:

Aug 23, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University of California, San Francisco

Trauma

Platelets

Coagulopathy

Additional relevant MeSH terms:

Wounds and Injuries

Study Results

No Results Posted as of Aug 23, 2021