Platelet REactivity in Sepsis Syndrome (PRESS)

NCT02562261 | Completed DMC

• 1 other identifier: 24958/19-12-13
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis Syndrome

Keywords

sepsis; platelet; platelet reactivity; P2Y12

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Serum levels of pro-inflammatory mediators in various study groups

  1 month to 1 year

• Correlation between serum levels of pro-inflammatory mediators and measured PRU between various study groups

  1 month to 1 year

• Repeated measurement of PRU in the same subject when transiting from one group to another

  1 hour to 1 month

Study Arms (4)

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 1. Temperature of \<36 °C (96.8 °F) or \>38 °C (100.4 °F) 2. Heart rate \>90bpm 3. Respiratory rate \>20/min or PaCO2\<32 mmHg (4.3 kPa) 4. 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.

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• healthy subjects
• Signed informed consent

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

University Hospital of Patras

Pátrai, Achaia, 26504, Greece

Location

Related Links

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

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Sepsis

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Infections

Study Officials

• Charalampos Gogos, MD,PhD

  University Hospital of Patras

  STUDY DIRECTOR

• Karolina Akinosoglou, MD,PhD

  University Hospital of Patras

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Internal Medicine and Infectious Diseases

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: September 29, 2015
• Study Start: January 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: October 23, 2018

Record last verified: 2018-10

Locations

GR (1)