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

NCT ID: NCT05218369

Last Updated: 2023-04-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-02-06

Study Completion Date

2024-12-01

Brief Summary

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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

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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.

Conditions

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COVID-19 Critical Illness

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

IL6 Antagonist

Intervention Type DRUG

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

Interventions

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IL6 Antagonist

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pecs

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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

Pécs, Baranya, Hungary

Site Status RECRUITING

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

Székesfehérvár, Fejér, Hungary

Site Status RECRUITING

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

Kistarcsa, Pest County, Hungary

Site Status RECRUITING

Countries

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Hungary

Central Contacts

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Péter Hegyi, MD, PhD, Dsc, MAE

Role: CONTACT

+3672/536-246

Szilárd Váncsa, MD

Role: CONTACT

+3672/536-246

Facility Contacts

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Tamás Kiss, MD

Role: primary

Margit Csata, MD

Role: backup

Máté Rottler, MD

Role: primary

Marcell Virág, MD

Role: backup

Zoltán Ruszkai, MD

Role: primary

Csanád Geréd, MD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 32651579 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30642917 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34288441 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32073213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32407672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27561337 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33161150 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36332964 (View on PubMed)

Related Links

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Other Identifiers

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1405-3/2022/EÜIG

Identifier Type: -

Identifier Source: org_study_id

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