Pro-inflammatory Role of Blood Platelets in Critically Ill Patients With Septic Shock. (PLAQSIS)

Pro-inflammatory Role of Blood Platelets in Critically Ill Patients With Septic Shock: an Observational Study.

Blood platelets play a major role in the inflammatory response. A dysregulation of platelets activation may be one of the contributors to tissue damage in critically ill patients with septic shock. The main objective of this study is to compare platelet activation markers levels (including plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1) at the early phase of a septic shock and a systemic inflammatory response syndrome (SIRS).

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Other: Septic shock; Other: Systemic Inflammatory Response Syndrome

Detailed Description

Sepsis is defined as life-threatening organ dysfunction due to dysregulated host response to infection which can lead to many failures of vital organs (kidneys, lungs, liver) in critically ill patients. It is accompanied at an early phase by both a proinflammatory and procoagulant state generating many platelet activators. Given their essential role in the inflammatory response, a dysregulation of platelets activation may be one of the contributors to tissue damage. To determine if platelet activation contribute to deregulation of the inflammatory response of the host in sepsis, the main objective of this study is to compare platelet activation markers levels of patients with septic shock and after major surgery. Plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha, HMGB-1, monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be studied and compared at inclusion (Day 0), Day 1 and Day 5.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Antoine DEWITTE, Dr; Phone Number: +33 5 57 65 68 66; Email: antoine.dewitte@chu-bordeaux.fr
• Study Contact Backup: Name: Alexandre OUATTARA, Pr; Phone Number: +33 5 57 65 68 66; Email: alexandre.ouattara@chu-bordeaux.fr

Study Locations

• France
  • Paris, France, 75010
    • Withdrawn
    • Hopital Saint Louis
  • Pessac, France, 33604
    • Recruiting
    • Hopital Haut Leveque
    • Contact: Antoine DEWITTE, Dr; Phone Number: +33 5 57 65 68 66; Email: antoine.dewitte@chu-bordeaux.fr
    • Contact: Alexandre OUATTARA, Pr; Phone Number: +33 5 57 65 68 66; Email: alexandre.ouattara@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

In this study, two populations will be recruiting, patients presenting a septic shock and patient presenting a SIRS, who will be admitted in intensive care unit or in continuing care units.

Description

Inclusion Criteria:

• Patients aged over 18 years admitted to an intensive care unit for:

  • a septic shock evolving for less than 24h (defined by an increase in the SOFA (Sequential Organ Failure Assessment) score of at least 2 points related to an infection, a persisting hypotension requiring vasopressors to maintain MAP ≥65 mmHg and a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation)
  • Or a systemic inflammatory response syndrome (SIRS) evolving for less than 24h (defined as 2 or more of the following variables: fever of more than 38°C or less than 36°C, heart rate of more than 90 beats per minute, respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO2) of less than 32 mm Hg, abnormal white blood cell count (>12,000/µL or <4,000/µL or >10% immature forms).

Exclusion Criteria:

• Age < 18 years
• Known history of constitutional thrombopathy (Bernard Soulier's disease, Glanzmann thrombasthenia, Gray's syndrome or dense granule disease)
• Myeloproliferative or myelodysplastic syndrome
• Autoimmune thrombocytopenic purpura
• Acute leukemia
• Haemorrhagic shock
• Platelet transfusion within 7 days prior to inclusion
• Antiplatelet medication (clopidogrel or ticagrelor taken within 5 days of inclusion, prasugrel or dipyridamole within 7 days of inclusion)
• Active HIV infection or known active hepatitis B or C
• Pregnant or breastfeeding woman
• Patients protected by the law, under guardianship or trusteeship, or deprived of liberty
• Patients without health insurance

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic shock; Plasma of 100 patients presenting a septic shock will be analysed including plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1	Other: Septic shock; Plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha, HMGB-1, monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be studied and compared at inclusion (Day 0), Day 1 and Day 5.
Systemic Inflammatory Response Syndrome; Plasma of 100 patient presenting a systemic inflammatory response syndrome = SIRS will be analysed including plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1	Other: Systemic Inflammatory Response Syndrome; Plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha, HMGB-1, monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be studied and compared at inclusion (Day 0), Day 1 and Day 5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration	Plasma concentration in CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1 will be measured in each group by dosage	Day 0, day 1 and day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Extracellular Traps formation	Monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be measured in each group by dosage	Day 0, day 1 and day 5
Markers of platelet activation and severity of organ failure	Correlation between markers of platelet activation and severity of organ failure will be measured by Sequential Organ Failure Assessment (SOFA) score. The score varies from 0 to 4.	Day 0 and Day 7
Markers of platelet activation and inflammatory markers	Correlation between markers of platelet activation and inflammatory markers (leukocytes and CRP) will be measured by KDIGO score.The score varies from 1 to 4.	Day 0 and Day 7
Markers of platelet activation and ISTH score	Correlation between markers of platelet activation and ISTH score of the International Society of Thrombosis and Haemostasis (ISTH) will be measured by Coagulation Intra Vasculaire Disséminée score. The score varies from < 5 to ≥ 5 : If score ≥ 5: compatible with a CIVD patent. If score <5: suggests a latent DIC.	Day 0
Markers of platelet activation and platelet count	Correlation between markers of platelet activation (CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1) and platelet count.	Day 0 and day 7
Markers of platelet activation on ICU mortality	Prognostic aspect of markers of platelet activation (CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1) on ICU mortality, hospital mortality, ICU and hospital length of stay, norepinephrine, kidney failure and ventilation free days.	Day 0 and Day 7
Levels of platelet activation markers	Correlation between levels of platelet activation markers studied (CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1).	Day 0 and Day 7

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: MSD France
• Investigators: Principal Investigator: Antoine DEWITTE, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2020
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Organ Failure; Blood platelets; CD40 ligand
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: CHUBX 2017/20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No