Clinical trial NCT05218369: Interleukin-6 Antagonists in Critically-ill Covid-19 Patients
Official title: Effects of Immunomodulation With Interleukin-6 Antagonists on the Coagulation System in Critically-ill Covid-19 Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Critical Illness
Keywords: severe COVID-19
interleukin-6 antagonist
ClotPro
viscoelastic hemostasis assay
Lead sponsor: University of Pecs
Sponsor class: OTHER
First posted: 2022-02-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All adult patients admitted to intensive care units (ICUs) requiring mechanical ventilation with proven COVID-19 infection and treated with interleukin-6 antagonist therapy.

Brief summary: The emerging SARS-COV2 virus has shed a new light on the cross-talks between the immune and the hemostatic system. In this study we aim to evaluate the dynamic change in coagulation caused by the modulation of the inflammatory response by interleukin-6 antagonist as assessed by viscoelastic methods in critically ill COVID-19 patients. Furthermore we try to draw attention to possible associations between the endothelial cell injury, inflammation and coagulation.

Detailed description: The emerging SARS-COV2 virus has shed new light on the cross-talk between the immune and the hemostatic system. Pathophysiologically in COVID-19 infection the thrombo-inflammatory process is initiated by the host's exaggerated systemic inflammatory response, also called "dysregulated immune response" that activates both the inflammatory and the coagulation cascade directly by inflammatory mediators and indirectly by causing endothelial cell injury. These mechanisms altogether contribute to the imbalance of the hemostasis that is characterized by a procoagulant state.

In this multicenter prospective observational study, we aim to evaluate the dynamic change in coagulation as a result of immunomodulation by interleukin-6 antagonists in critically ill COVID-19 patients. We will assess the hemostatic system by a viscoelastic hemostasis assay (Clotpro, Haemonetics Corporation, Boston). Furthermore, we try to draw attention to possible associations between endothelial cell injury, inflammation, and coagulation. To compare these parameters we will draw blood for analysis before administration of IL-6 antagonist then 24h after, 48h after, and 7 days after.

Eligibility criteria: Inclusion Criteria:

* Adults (\>18 years old)
* Clinical diagnosis of SARS-CoV2 infection with rtPCR confirmation
* Disease severity with the indication of immunomodulation therapy with interleukin-6 antagonist: acute respiratory failure that requires invasive, noninvasive ventilation , or high flow nasal oxygen therapy with the following parameters: FiO2 \> 0,4, flow \> 30L/min and C Reactive Protein \> 75 mg/L

Exclusion Criteria:

* The patient had previously been administered one of the following immunomodulating drug: anakinra, tocilizumab, sarilumab
* Presence of any condition or drug in the medical history that can lead to immunosuppression
* Suspicion of infection (active tuberculosis, bacterial, viral, fungal) or level of procalcitonine higher than 0,5 ng/ml at the enrollment of the patient
* Number of thrombocyte lower than 50 x 109 / L
* More than \>120 hours passed between the admission to the ICU and the administration of interleukin-6 antagonist
* Administration of any of the following drugs the week before or during the study: fibrinolytic therapy, factor products (PCC, ATIII, FVIIa, FXIII), fibrinogen, desmopressin, tranexamic acid, blood products (FFP, thrombocyte concentrate)
* Pregnancy
* The patient or his legal guardian does not sign the consent

Primary outcomes:
measure: Change in the lysis time
timeFrame: 48 hours
measure: Change in the lysis onset time
timeFrame: 48 hours
Secondary outcomes:
measure: Change in the lysis time
timeFrame: 24 hours and 7 days
measure: Change in the lysis onset time
timeFrame: 24 hours and 7 days
measure: Change in Clotpro assay
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between procalcitonin and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between C reactive protein and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between ferritin and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between lactate dehydrogenase and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between syndecan-1 and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
measure: Correlation between thrombomodulin and Clotpro
timeFrame: 24 hours, 48 hours, and 7 days
Other outcomes:
Locations:
city: Pécs
country: Hungary
facility: Department of Anaesthesiology and Intensive Therapye, Medical School, University of Pécs
state: Baranya
city: Székesfehérvár
country: Hungary
facility: Central Department of Anesthesiology and Intensive Care, Szent György University Teaching Hospital of County Fejér
state: Fejér
city: Kistarcsa
country: Hungary
facility: Department of Anaesthesiology and Intensive Therapy, Pest Megyei Flór Ferenc Hospital
state: Pest
Study officials:
References:
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