Evaluation of Interleukine 6 (and Other Cytokines and Inflammatory Markers) in COVID-19 Patients With a Systemic Inflammatory Response Syndrome

NCT04346017 | Completed

• 1 other identifier: CHUB-IL6-COVID-19
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

In patients infected by the SARS-Cov-2 Coronavirus a severely progressive disease requiring hospitalization in intensive care seems related to deregulation of cytokines with very high levels of IL-6, IL-2, IL-7, IL-10 and TNF-α. In order to elucidate the mechanism of this hyper inflammatory syndrome we will measure a panel of pro and anti inflammatory cytokines, as well as known markers of macrophage activation syndrome. To determine the role of activation of the complement cascade the most important complement factors and their activation markers will be measured. The changes of those parameters will be monitored after administration of an anti-IL6R antibody therapy.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (6)

• IL6 concentration

  Interleukine 6, soluble IL6-R, complex IL6-IL6R concentration

  Before anti-IL6R treatment (baseline)

• IL6 concentration change from baseline value

  Interleukine 6 soluble IL6-R, complex IL6-IL6R variation compared to baseline value

  Twice a week from day 1 to day 14 post anti-IL6R administration

• Complement parameters

  CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2

  Before anti-IL6R treatment (baseline)

• Complement parameters change from baseline values

  CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2 variation compared to baseline values

  Twice a week from day 1 to day 14 post anti-IL6R administration

• Inflammatory cytokines baseline concentrations

  Concentration of TNFa, IFNg, IL1, IL7, IL10, IL12, IL17, IL18

  Before anti-IL6R treatment (baseline)

• Inflammatory cytokines change from baseline values

  Concentration of TNFa, IFNg, IL1, IL7, IL10, IL12, IL17, IL18 variation compared to baseline values

  Twice a week from day 1 to day 14 post anti-IL6R administration

Secondary Outcomes (2)

• Concentration of markers of macrophage activation

  Before anti-IL6R treatment (baseline)

• Markers of macrophage activation change from baseline values

  Twice a week from day 1 to day 14 post anti-IL6R administration

Study Arms (2)

Ventilation support

EXPERIMENTAL

The experimental group will include Covid-19 infected patients with non-invasive or invasive ventilation support (BCRSS score ≥3).

Diagnostic Test: Cytokines dosage; Diagnostic Test: Complement dosage

Control group

OTHER

The control group will include Covid-19 infected patients who don't have respiratory problems justifying a transfer to intensive care.

Diagnostic Test: Cytokines dosage; Diagnostic Test: Complement dosage

Interventions

Cytokines dosage DIAGNOSTIC_TEST

Dosage of inflammatory cytokines and other markers of systemic inflammatory syndromes (TNFa, IFNg, IL1, IL7, IL10, IL12, IL17, sCD25, sCD163, sCD14, IL-6, IL6-R, complex IL6-IL6R, glycolsylated ferritin...).

Control group; Ventilation support

Complement dosage DIAGNOSTIC_TEST

Dosage of the complement parameters: CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2.

Control group; Ventilation support

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• End of the initial phase of high viral load of SARS-Cov-2 (for example apyretic\> 72h and / or at least 7 days after the onset of symptoms)
• Worsening of respiratory exchanges which require non-invasive or invasive ventilation support (BCRSS score ≥3)
• High levels of IL-6 (\> 40 pg / ml); alternatively high levels of d-dimer and / or PCR and / or ferritin and / or fibrinogen gradually increase.
• A control group will be formed by patients in the Covid unit who do not have respiratory problems justifying a transfer to intensive care.

You may not qualify if:

• Documented sepsis caused by other pathogens other than SARS-Corv-2.
• Presence of comorbidities likely to lead, according to clinical judgment, to an unfavorable result
• Immunosuppressive anti-rejection therapy

Sponsors & Collaborators

• Francis Corazza: lead

Study Sites (1)

CHU Brugmann

Brussels, 1020, Belgium

Location

Related Publications (1)

• Ponthieux F, Dauby N, Maillart E, Fils JF, Smet J, Claus M, Besse-Hammer T, Bels D, Corazza F, Nagant C. Tocilizumab-Induced Unexpected Increase of Several Inflammatory Cytokines in Critically Ill COVID-19 Patients: The Anti-Inflammatory Side of IL-6. Viral Immunol. 2022 Jan-Feb;35(1):60-70. doi: 10.1089/vim.2021.0111. Epub 2022 Jan 27.

  PMID: 35085462 DERIVED

MeSH Terms

Conditions

COVID-19

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Immunology Laboratory

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 15, 2020
• Study Start: March 20, 2020
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)