Platelet REactivity in Sepsis Syndrome (PRESS)

Sponsor

Charalambos .A. Gogos (Other)

Overall Status

Completed

CT.gov ID

NCT02562261

Collaborator

Hellenic Society for Chemotherapy : Hellenic Sepsis Study Group (Other), University Hospital of Patras (Other)

140

Enrollment

Location

Actual Duration (Months)

8.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sepsis Syndrome

Study Design

Study Type:

Observational

Actual Enrollment :

140 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Platelet Reactivity During Different Stages of Sepsis

Actual Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

P2Y12 mediated Platelet Reactivity on presentation [0 hours post 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
Comparison of P2Y12 mediated Platelet Reactivity between study groups [at 1 year]
Measurements of P2Y12 mediated platelet reactivity of different study groups that have taken place on presentation will be compared following completion of study recruitment

Secondary Outcome Measures

Serum levels of pro-inflammatory mediators in various study groups [1 month to 1 year]
Patient serum will be collected and cytokines will be measured in all patients
Correlation between serum levels of pro-inflammatory mediators and measured PRU between various study groups [1 month to 1 year]
Following measurement of serum cytokines (outcome 3), assessment of potential correlation with PRU will be performed
Repeated measurement of PRU in the same subject when transiting from one group to another [1 hour to 1 month]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Patras	Patras	Achaia	Greece	26504

Sponsors and Collaborators

Charalambos .A. Gogos
Hellenic Society for Chemotherapy : Hellenic Sepsis Study Group
University Hospital of Patras

Investigators

Study Director: Charalampos Gogos, MD,PhD, University Hospital of Patras
Principal Investigator: Karolina Akinosoglou, MD,PhD, University Hospital of Patras