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

NCT05218369 | Unknown DMC

• 1 other identifier: 1405-3/2022/EÜIG
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

COVID-19; Critical Illness

Keywords

severe COVID-19; interleukin-6 antagonist; ClotPro; viscoelastic hemostasis assay

Outcome Measures

Primary Outcomes (2)

• Change in the lysis time

  Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis time (LT).

  48 hours

• Change in the lysis onset time

  Change of the fibrinolytic system before (T0) and after immunomodulation therapy, measured by the lysis onset time (LOT).

  48 hours

Secondary Outcomes (9)

• Change in the lysis time

  24 hours and 7 days

• Change in the lysis onset time

  24 hours and 7 days

• Change in Clotpro assay

  24 hours, 48 hours, and 7 days

• Correlation between procalcitonin and Clotpro

  24 hours, 48 hours, and 7 days

• Correlation between C reactive protein and Clotpro

  24 hours, 48 hours, and 7 days

Study Arms (1)

Critically ill COVID-19 patients

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.

Drug: IL6 Antagonist

Interventions

IL6 Antagonist DRUG

Patients will receive IL-6 antagonist therapy at the consultant's discretion.

Critically ill COVID-19 patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pecs: lead

Study Sites (3)

Department of Anaesthesiology and Intensive Therapye, Medical School, University of Pécs

Pécs, Baranya, 7624, Hungary

RECRUITING

Central Department of Anesthesiology and Intensive Care, Szent György University Teaching Hospital of County Fejér

Székesfehérvár, Fejér, 8000, Hungary

RECRUITING

Department of Anaesthesiology and Intensive Therapy, Pest Megyei Flór Ferenc Hospital

Kistarcsa, Pest County, 2143, Hungary

RECRUITING

Related Publications (9)

• Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Extrapulmonary manifestations of COVID-19. Nat Med. 2020 Jul;26(7):1017-1032. doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10.

  PMID: 32651579 BACKGROUND

• Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019 Feb 28;133(9):906-918. doi: 10.1182/blood-2018-11-882993. Epub 2019 Jan 14.

  PMID: 30642917 BACKGROUND

• Levy JH, Iba T, Olson LB, Corey KM, Ghadimi K, Connors JM. COVID-19: Thrombosis, thromboinflammation, and anticoagulation considerations. Int J Lab Hematol. 2021 Jul;43 Suppl 1(Suppl 1):29-35. doi: 10.1111/ijlh.13500.

  PMID: 34288441 BACKGROUND

• Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.

  PMID: 32073213 BACKGROUND

• Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438-e440. doi: 10.1016/S2352-3026(20)30145-9. Epub 2020 May 11. No abstract available.

  PMID: 32407672 BACKGROUND

• Bester J, Pretorius E. Effects of IL-1beta, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep. 2016 Aug 26;6:32188. doi: 10.1038/srep32188.

  PMID: 27561337 BACKGROUND

• Tleyjeh IM, Kashour Z, Damlaj M, Riaz M, Tlayjeh H, Altannir M, Altannir Y, Al-Tannir M, Tleyjeh R, Hassett L, Kashour T. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect. 2021 Feb;27(2):215-227. doi: 10.1016/j.cmi.2020.10.036. Epub 2020 Nov 5.

  PMID: 33161150 BACKGROUND

• Kovacs EH, Rottler M, Ruszkai Z, Gered C, Kiss T, Csata M, Reger B, Jakabfi-Csepregi R, Papp I, Turan C, Hegyi P, Fazakas J, Molnar Z, Tanczos K. Exploratory Analysis of Coagulation and Fibrinolysis Trajectories After IL-6 Antagonist Therapy in COVID-19: A Case Series. Biomedicines. 2026 Jan 22;14(1):254. doi: 10.3390/biomedicines14010254.

  PMID: 41595788 DERIVED

• Kovacs EH, Rottler M, Dembrovszky F, Ocskay K, Szabo L, Hegyi P, Molnar Z, Tanczos K. Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study. BMJ Open. 2022 Nov 4;12(11):e063856. doi: 10.1136/bmjopen-2022-063856.

  PMID: 36332964 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

COVID-19; Critical Illness

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Péter Hegyi, MD, PhD, Dsc, MAE

CONTACT

+3672/536-246; p.hegyi@tm-centre.org

Szilárd Váncsa, MD

CONTACT

+3672/536-246; vancsaszilard@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2022
• First Posted: February 1, 2022
• Study Start: February 6, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 1, 2024
• Last Updated: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (3)