Platelet REactivity in Sepsis Syndrome (PRESS) (PRESS)

Platelet Reactivity During Different Stages of Sepsis

Activation of blood platelets is a typical finding in patients with systemic inflammation and sepsis.They seem to mediate key pro-inflammatory mediator secretion, immune-cell activation while their adhesion to the endothelium enhances the pro-coagulatory activity of endothelial cells impairing microcirculation thus, may lead to multiple organ dysfunction. However, the exact effects of bacterial products on platelet function have not been found to be consistent and may vary according to the species, the timing of the study, and the pathogenesis of sepsis. Data vary, including both increased and decreased platelet reactivity and aggregation among patients with sepsis compared to healthy controls. Defining platelet's behaviour during sepsis is particularly important in view of recent findings revealing potential association between antiplatelet therapy and reduction in short term mortality, incidence of acute lung injury and intensive care unit admission in critically ill patients.This study aims to measure P2Y12 mediated platelet reactivity, -using the point-of-care P2Y12 VerifyNow assay, in platelet reactivity units (PRU)- along different stages of sepsis, including bacteremia/uncomplicated infection, sepsis, severe sepsis and septic shock. Subgroup follow up of patients going along different stages will also be performed. At the end of this study analysis of clinical and laboratory findings in correlation with platelet reactivity will be performed to assess platelet aggregation during sepsis.

Study Overview

• Status: Completed
• Conditions: Sepsis Syndrome

• Study Type: Observational
• Enrollment (Actual): 140

Contacts and Locations

Study Locations

• Greece
  • Achaia
    • Patras, Achaia, Greece, 26504
      • University Hospital of Patras

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Within 0-8 hours of presentation in emergency department patients will be assessed and assigned upon their health status in four distinct groups of uncomplicated infection/bacteraemia , sepsis, severe sepsis/septic shock as this is defined by International Sepsis Definitions Conference. Thirty five healthy volunteers will serve as a control group.

Description

Inclusion Criteria:

• Patients presenting 0-8 hours post admission with signs of one of the following i) uncomplicated infection/bacteremia ii) sepsis iii) severe sepsis iv) septic shock
• 30 healthy subjects
• Signed informed consent

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Inability to give informed consent
• PLTs<70.000/ul or PLTs>741.000 ul
• Ht<25% or Ht>52%
• History of P2Y12 or GPIIb/IIIainhibitors the last 15 days prior assortment
• Patients with inherited (vonWillebrand factor deficiency, Glanzmann thrombasthenia, Bernard-Sulier syndrome) or established acquired platelet disorders (HIT)
• Patients undergoing hemodialysis
• History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
• Previous history of immunologic disease (neoplasm, autoimmune disorders, HIV)
• Subjects receiving daily treatment with immune-modulating regimens.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Healthy
Uncomplicated Infection; Showing signs of infection as defined by International Sepsis Definitions Conference 2003
Sepsis; Sepsis is defined as systemic inflammatory response syndrome (i.e. presence of two or more of the following; Temperature of <36 °C (96.8 °F) or >38 °C (100.4 °F); Heart rate >90bpm; Respiratory rate >20/min or PaCO2<32 mmHg (4.3 kPa); WBC <4x109/L (<4000/mm³), >12x109/L (>12,000/mm³), or 10% bands in response to an infectious process..
Severe Sepsis/Septic Shock; Severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion [manifesting as hypotension, elevated lactate (serum lactate 2 times the upper limit of normal), or decreased urine output (urine output < 0.5 ml/kg/hr)] Septic shock is defined as severe sepsis plus persistently low blood pressure (< 5th percentile for age or systolic blood pressure < 2 standard deviations below normal for age) following the administration of intravenous fluids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
P2Y12 mediated Platelet Reactivity on presentation	Measurement of P2Y12 mediated platelet reactivity of patients in different study groups i.e healthy controls, uncomplicated infection, sepsis, severe sepsis/septic shock in P2Y12 reactivity units (PRU). PRU measurement will take place on time of presentation and recognition of signs of infection	0 hours post presentation
Comparison of P2Y12 mediated Platelet Reactivity between study groups	Measurements of P2Y12 mediated platelet reactivity of different study groups that have taken place on presentation will be compared following completion of study recruitment	at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of pro-inflammatory mediators in various study groups	Patient serum will be collected and cytokines will be measured in all patients	1 month to 1 year
Correlation between serum levels of pro-inflammatory mediators and measured PRU between various study groups	Following measurement of serum cytokines (outcome 3), assessment of potential correlation with PRU will be performed	1 month to 1 year
Repeated measurement of PRU in the same subject when transiting from one group to another	Patients transiting from one stage of sepsis to another (for example severe sepsis to healthy state OR from uncomplicated infection to sepsis) will be repetitively measured to assess platelet reactivity alteration	1 hour to 1 month

Collaborators and Investigators

• Sponsor: Charalambos .A. Gogos
• Collaborators: University Hospital of Patras; Hellenic Society for Chemotherapy : Hellenic Sepsis Study Group
• Investigators: Study Director: Charalampos Gogos, MD,PhD, University Hospital of Patras; Principal Investigator: Karolina Akinosoglou, MD,PhD, University Hospital of Patras

Publications and helpful links

Helpful Links

• Platelet reactivity in sepsis syndrome: results from the PRESS study

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 15, 2015
• First Submitted That Met QC Criteria: September 26, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: platelet; sepsis; platelet reactivity; P2Y12
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease; Shock; Sepsis; Toxemia; Syndrome; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 24958/19-12-13