Interleukin-6 Antagonists in Critically-ill Covid-19 Patients

Recruiting

• Conditions: COVID-19; Critical Illness
• Interventions: Drug: IL6 Antagonist

• Registration Number: NCT05218369
• Lead Sponsor: University of Pecs

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.

Study Timeline

• Study First Submitted: 2022-01-29
• Study First Submitted QC: 2022-01-29
• Study First Posted: 2022-02-01
• Study Start: 2022-02-06
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-18
• Last Update Posted: 2023-04-20
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Critically ill COVID-19 patients	IL6 Antagonist	Patients in ICU due to critical COVID-19 infection, who receive early (within the first 24 hours, but no later than 48 hours after intubation) IL-6 antagonist therapy at the consultant's discretion.

Primary Outcome Measures

Name	Time	Method
Change in the lysis time	48 hours	Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis time (LT).
Change in the lysis onset time	48 hours	Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis onset time (LOT).

Secondary Outcome Measures

Name	Time	Method
Change in the lysis time	24 hours and 7 days	Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis time (LT).
Change in the lysis onset time	24 hours and 7 days	Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis onset time (LOT).
Change in Clotpro assay	24 hours, 48 hours, and 7 days	Change in blood coagulation parameters which evaluate hypercoagulable state before (T0) and after immunomodulation therapy (T1,2,3) measured by Clotpro device assays.
Correlation between procalcitonin and Clotpro	24 hours, 48 hours, and 7 days	Correlation between inflammatory and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the inflammatory laboratory parameters as procalcitonin and the blood coagulation parameters measured by the Clotpro.
Correlation between C reactive protein and Clotpro	24 hours, 48 hours, and 7 days	Correlation between inflammatory and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the inflammatory laboratory parameters as C reactive protein and the blood coagulation parameters measured by the Clotpro.
Correlation between ferritin and Clotpro	24 hours, 48 hours, and 7 days	Correlation between inflammatory and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the inflammatory laboratory parameters as ferritin and the blood coagulation parameters measured by the Clotpro.
Correlation between lactate dehydrogenase and Clotpro	24 hours, 48 hours, and 7 days	Correlation between inflammatory and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the inflammatory laboratory parameters as lactate dehydrogenase and the blood coagulation parameters measured by the Clotpro.
Correlation between syndecan-1 and Clotpro	24 hours, 48 hours, and 7 days	Correlation between biomarkers of endothelial injury and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the biomarkers of the endothelial damage as syndecan-1 and the blood coagulation parameters measured by the Clotpro.
Correlation between thrombomodulin and Clotpro	24 hours, 48 hours, and 7 days	Correlation between biomarkers of endothelial injury and blood coagulation parameters. For the assessment of this endpoint, we will use the results of the biomarkers of the endothelial damage as thrombomodulin and the blood coagulation parameters measured by the Clotpro.

Trial Locations

Locations (3)

Department of Anaesthesiology and Intensive Therapye, Medical School, University of Pécs; 🇭🇺 Pécs, Baranya, Hungary

Central Department of Anesthesiology and Intensive Care, Szent György University Teaching Hospital of County Fejér; 🇭🇺 Székesfehérvár, Fejér, Hungary

Department of Anaesthesiology and Intensive Therapy, Pest Megyei Flór Ferenc Hospital; 🇭🇺 Kistarcsa, Pest, Hungary