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

Completed

• Conditions: Septic Shock
• Interventions: Other: Systemic Inflammatory Response Syndrome; Other: Septic shock

• Registration Number: NCT04080453
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

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).

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 Timeline

• Study First Submitted: 2019-09-03
• Study First Submitted QC: 2019-09-03
• Study First Posted: 2019-09-06
• Study Start: 2020-11-09
• Primary Completion: 2024-02-09
• Status Verified: 2024-04
• Study Completion: 2024-04-25
• Last Update Submitted: 2024-04-25
• Last Update Posted: 2024-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 202

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Systemic Inflammatory Response Syndrome	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
Septic shock	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

Primary Outcome Measures

Name	Time	Method
Plasma concentration	Day 0, day 1 and day 5	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

Secondary Outcome Measures

Name	Time	Method
Markers of platelet activation and severity of organ failure	Day 0 and Day 7	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.
Markers of platelet activation and ISTH score	Day 0	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.
Neutrophil Extracellular Traps formation	Day 0, day 1 and day 5	Monocyte Dnases signal, circulating free DNA and DNase1 and DNase1L3 activities will be measured in each group by dosage
Markers of platelet activation and inflammatory markers	Day 0 and Day 7	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.
Markers of platelet activation on ICU mortality	Day 0 and Day 7	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.
Levels of platelet activation markers	Day 0 and Day 7	Correlation between levels of platelet activation markers studied (CD154, beta thromboglobulin, platelet factor 4, platelet microparticles, soluble CD62, RANTES, GRO-alpha and HMGB-1).
Markers of platelet activation and platelet count	Day 0 and day 7	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.

Trial Locations

Locations (1)

Hôpital Haut Lévêque; 🇫🇷 Pessac, France