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PLatelets Acetyl-CoA Carboxylase Phosphorylation State in SEPtic Shock (PLACCSEPS)

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ClinicalTrials.gov Identifier: NCT04107402
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary:
Knowing the dramatic increase in thrombin generation during sepsis, our research hypothesis is that AMPK-induced ACC phosphorylation in platelets is increased and that this might modulate platelets metabolism and more particularly platelets inflammatory mediators content, coming from AA and lipids.

Condition or disease Intervention/treatment Phase
Septic Shock Platelet Signal Processing Defect Inflammatory Response Disseminated Intravascular Coagulation Covid19 Neutrophil Extracellular Trap Formation Other: Assessment of coagulopathy, Platelets activation and Platelets-Neutrophils interplay Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Prospective Evaluation of PLatelets Acetyl-CoA Carboxylase Phosphorylation State in SEPtic Shock Patients. Impact of Platelets Metabolism to Inflammatory Response.
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : March 15, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: Septic shock
Septic shock Patients admitted to the ICU
Other: Assessment of coagulopathy, Platelets activation and Platelets-Neutrophils interplay
Blood sample Urine Sample Pulmonary, hepatic and cardiac tissue from biopsy and autopsy
Other Names:
  • Inflammatory biomarkers
  • Coagulation assessment
  • Platelets activation state assessment
  • Neutrophils Extra-cellular trap assessment
  • Quantification and analysis of micro-thrombi
  • Platelets Acetyl-CoA Carboxylase phosphorylation analysis

Control group
Patients recruited at the central lab of the hospital, with matched age, gender and comorbidities
Other: Assessment of coagulopathy, Platelets activation and Platelets-Neutrophils interplay
Blood sample Urine Sample Pulmonary, hepatic and cardiac tissue from biopsy and autopsy
Other Names:
  • Inflammatory biomarkers
  • Coagulation assessment
  • Platelets activation state assessment
  • Neutrophils Extra-cellular trap assessment
  • Quantification and analysis of micro-thrombi
  • Platelets Acetyl-CoA Carboxylase phosphorylation analysis

Experimental: Covid-19
Covid-19 patients admitted to the ICU for Acute Respiratory Distress Syndrom with PaO2/FiO2 < 200
Other: Assessment of coagulopathy, Platelets activation and Platelets-Neutrophils interplay
Blood sample Urine Sample Pulmonary, hepatic and cardiac tissue from biopsy and autopsy
Other Names:
  • Inflammatory biomarkers
  • Coagulation assessment
  • Platelets activation state assessment
  • Neutrophils Extra-cellular trap assessment
  • Quantification and analysis of micro-thrombi
  • Platelets Acetyl-CoA Carboxylase phosphorylation analysis




Primary Outcome Measures :
  1. Platelets Acetyl-CoA Carboxylase phosphorylation rate [ Time Frame: At the time of inclusion ]
    ACC phosphorylation on Ser79 (phosphoACC) in platelets of patients will be assessed using western blotting. Results will be expressed in arbitrary units (A.U). A signal above 0.5 A.U. has already been shown to be above 2 standard deviation in a healthy population.


Secondary Outcome Measures :
  1. Sepsis severity [ Time Frame: At the time of inclusion ]
    Sepsis severity will be assessed using the SOFA score (Sepsis-related Organ Failure Assessment). Range from 0( less severe) to 24 (more severe).

  2. Sepsis severity [ Time Frame: At the time of inclusion ]
    Sepsis severity will be assessed using the APACHE II score) Acute Physiology And Chronic Health Evaluation) Range 0 (less severe) to 299 (more severe).

  3. Mortality rate [ Time Frame: 30 days and 1-year follow-up ]
  4. Platelet function assessment [ Time Frame: At the time of inclusion ]
    Platelet function will be assessed using platelets aggregometry. The Aggregation (in AU), the maximum height of the curve during the measurement period will be assessed.

  5. Platelet function assessment [ Time Frame: At the time of inclusion ]
    Platelet function will be assessed using platelets aggregometry. Area Under the aggregation Curve (AUC) will be assessed and recorded as Units or U.

  6. Platelet function assessment [ Time Frame: At the time of inclusion ]
    Platelet function will be assessed using platelets aggregometry. Velocity (in AU/min), the maximum slope of the curve will be assessed.

  7. Thrombin generation marker rate [ Time Frame: At the time of inclusion ]
    D-Dimers (ng/ml)

  8. Thrombin generation marker rate [ Time Frame: At the time of inclusion ]
    Urinary Thrombin-antithrombin complex (ng/mL)

  9. Tubulin acetylation rate [ Time Frame: At the time of inclusion ]
    Tubulin acetylation will be assessed using western blotting. Results will be expressed in arbitrary units (A.U).

  10. Total platelets lipid content and composition [ Time Frame: At the time of inclusion ]
    Total platelets lipid content and composition will be assessed using metabolomics approach by Mass Spectrometry. Fold-change estimates and corresponding P values were derived from regression models for each lipid species and each predictor. To control for multiple testing, all P values will be further adjusted for Benjamini-Hochberg false discovery rate (FDR), with a FDR <0.05 considered statistically significant

  11. Neutrophils extracellular trap formation [ Time Frame: At the time of inclusion ]
    Myeloperoxidase MPO (ng/mL)

  12. Neutrophils extracellular trap formation [ Time Frame: At the time of inclusion ]
    Citrulinated Histon 3 H3-Cit (ng/mL)

  13. Platelets activation [ Time Frame: At the time of inclusion ]
    Soluble CD62P (ng/mL)

  14. Respiratory failure [ Time Frame: At the time of inclusion and through study completion up to day 30 ]
    PaO2/FiO2



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Informed consent of patients, their relatives or independent physician
  • Septic shock defined as a sepsis with vasopressor therapy needed to elevate MAP ≥65 mmHg, and lactate > 2 mmol/L, despite adequate fluid resuscitation of 30mL/kg of intravenous crystalloid within 6 hours. Inclusion within 48 hours of ICU admission.
  • Covid-19 patients with ARDS and PaO2/FiO2 < 200. Inclusion within 5 days after ICU admission.

Exclusion Criteria:

  • Patients on therapeutic anticoagulation therapy (oral or parenteral) including heparins, fondaparinux, vitamin K antagonist, novel oral anticoagulants, for any reasons DESPITE therapeutic anticoagulation as a treatment for Covid-19 patients.
  • Recent (less than 1 month) chemotherapy
  • Active inflammatory disease
  • Haemophilia and other coagulopathy
  • Previous history of thrombocytopenia (<100 000 platelets/mm3)
  • Cirrhosis (Child Plug > A)
  • Recent (less than 48 hours) major surgery

Exclusion criteria for Covid-19 patients:

- bacterial co-infection


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04107402


Contacts
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Contact: Melanie Dechamps, MD +3227642782 melanie.dechamps@uclouvain.be

Locations
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Belgium
Cliniques Universitaires St Luc Recruiting
Bruxelles, Belgium, 1200
Contact: Melanie Dechamps, MD    +3227642782    melanie.dechamps@uclouvain.be   
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
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Principal Investigator: Christophe Beauloye, MD Cliniques Universitaires St Luc
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Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT04107402    
Other Study ID Numbers: PLACCSEPS
2018/11DEC/469 ( Other Identifier: CEHF )
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Septic shock
Platelets
Acetyl CoA Carboxylase
Additional relevant MeSH terms:
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Shock, Septic
Disseminated Intravascular Coagulation
Shock
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Thrombophilia