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

Septic Shock Clinical Trial

— PLAQSIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04080453
• Other study ID #: CHUBX 2017/20
• Status: Completed
• Start date: November 9, 2020
• Est. completion date: April 25, 2024

Study information

• Verified date: April 2024
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: April 25, 2024
• Est. primary completion date: February 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

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 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.

Locations

Country	Name	City	State
France	Hôpital Haut Lévêque	Pessac

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	MSD France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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