COVID-19NCT04346017
Evaluation of Interleukine 6 (and Other Cytokines and Inflammatory Markers) in COVID-19 Patients With a Systemic Inflammatory Response Syndrome
A study testing Cytokines dosage and Complement dosage in people with COVID-19, run by Francis Corazza at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- COVID-19
- What is being tested?
- Cytokines dosage and Complement dosage
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteBelgium
- Study dates
- 20 Mar 2020to 23 Nov 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Interleukine 6 (and Other Cytokines and Inflammatory Markers) in SARS-Cov-2 Infected Patients With a Systemic Inflammatory Response Syndrome
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.
Read the detailed description
In patients with severely progressive SARS-Cov-2 Coronavirus infection, the elderly and immunocompromised are at greater risk of progressing to a serious image of ARDS (Acute Respiratory Distress syndrome). A recent study has shown that patients, sometimes young, requiring hospitalization in intensive care have deregulation of cytokines with very high levels of IL-6, IL-2, IL-7, IL-10 and TNF-α. The cytokines involved in the pathogenesis and clinical manifestations of CRS are mainly IL-6, gamma interferon (IFN-g), tumor necrosis factor alpha (TNF-a) and IL-10.
Although immunoinflammatory therapy is not systematically recommended in pneumonia linked to SARS-CoV-2, given the CRS and the pathophysiological results of pulmonary edema and the formation of the hyaline membrane, a targeted therapeutic approach and temporally accompanied by adequate ventilatory support could be beneficial in patients with severe pneumonia who develop ARDS. Tocilizumab (Roactemra®) is a drug that blocks the IL-6 receptor commonly prescribed for the treatment of rheumatoid arthritis. The intravenous formulation has been approved for the treatment of CRS which occurs during treatment with Car-T; given the clinical picture and cytokine levels in patients with severe SARS-Cov-2 pneumonia, Tocilizumab or another anti-IL6R antagonist may reasonably be expected to contribute to the control of virus-induced Systemic Inflammatory Response Syndrome (SIRS) in patients with elevated levels of IL-6.
The objectivation of high interleukin 6 levels in these patients should be an important scientific argument to justify the administration of therapy based on antagonization of IL6. Measurement of other pro inflammatory cytokines will shed light on the mechanism of the inflammatory syndrome induced by the SARS-CoV-2 virus.
One of the pathophysiological mechanisms of pulmonary pathology could be the induction of the production of complement factors by interleukin 6 as well as the activation of the complement cascade by the virus via the lectin pathway. It is known that one of the effects of Tocilizumab is to reduce the concentration of the various complement factors, the synthesis of which is under the control of interleukin 6. This is why this study proposes to measure certain parameters of the complement (CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2) in order to objectify and quantify this activation.
If the activation of the complement proves significant it could be an argument for a treatment targeting more specifically the cascade of the complement.
- Conditions
- COVID-19
- Being tested
- Cytokines dosage, Complement dosage
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytokines dosageDiagnostic 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...).
Complement dosageDiagnostic test
Dosage of the complement parameters: CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2.
| Study group | Role | What they receive |
|---|---|---|
| Ventilation support | Experimental | The experimental group will include Covid-19 infected patients with non-invasive or invasive ventilation support (BCRSS score ≥3). Receives: 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. Receives: Diagnostic Test: Cytokines dosage; Diagnostic Test: Complement dosage |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL6 concentration
Interleukine 6, soluble IL6-R, complex IL6-IL6R concentration
Measured: Before anti-IL6R treatment (baseline)
IL6 concentration change from baseline value
Interleukine 6 soluble IL6-R, complex IL6-IL6R variation compared to baseline value
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Twice a week from day 1 to day 14 post anti-IL6R administration
Secondary outcomes (2)
Concentration of markers of macrophage activation
sCD25, sCD163, sCD14, glycosylated ferritin
Measured: Before anti-IL6R treatment (baseline)
Markers of macrophage activation change from baseline values
sCD25, sCD163, sCD14, glycosylated ferritin variation compared to baseline values
Measured: Twice a week from day 1 to day 14 post anti-IL6R administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start20 Mar 2020
- Primary completion23 Nov 2020
- Study completion23 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Francis Corazza
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Francis Corazza, Brugmann University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04346017
- Sponsor's protocol ID
- CHUB-IL6-COVID-19
- Status last verified
- Sep 2021
- First submitted
- 13 Apr 2020
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35085462
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Interleukine 6 (and Other Cytokines and Inflammatory Markers) in SARS-Cov-2 Infected Patients With a Systemic Inflammatory Response Syndrome
- ClinicalTrials.gov ID
- NCT04346017
- Acronym / sponsor ID
- CHUB-IL6-COVID-19
- Conditions
- COVID-19
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Francis CorazzaUniversity, hospital or other
- Study start
- 20 Mar 2020 (actual)
- Primary completion
- 23 Nov 2020 (actual)
- Study completion
- 23 Nov 2020 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In patients with severely progressive SARS-Cov-2 Coronavirus infection, the elderly and immunocompromised are at greater risk of progressing to a serious image of ARDS (Acute Respiratory Distress syndrome). A recent study has shown that patients, sometimes young, requiring hospitalization in intensive care have deregulation of cytokines with very high levels of IL-6, IL-2, IL-7, IL-10 and TNF-α. The cytokines involved in the pathogenesis and clinical manifestations of CRS are mainly IL-6, gamma interferon (IFN-g), tumor necrosis factor alpha (TNF-a) and IL-10.
Although immunoinflammatory therapy is not systematically recommended in pneumonia linked to SARS-CoV-2, given the CRS and the pathophysiological results of pulmonary edema and the formation of the hyaline membrane, a targeted therapeutic approach and temporally accompanied by adequate ventilatory support could be beneficial in patients with severe pneumonia who develop ARDS. Tocilizumab (Roactemra®) is a drug that blocks the IL-6 receptor commonly prescribed for the treatment of rheumatoid arthritis. The intravenous formulation has been approved for the treatment of CRS which occurs during treatment with Car-T; given the clinical picture and cytokine levels in patients with severe SARS-Cov-2 pneumonia, Tocilizumab or another anti-IL6R antagonist may reasonably be expected to contribute to the control of virus-induced Systemic Inflammatory Response Syndrome (SIRS) in patients with elevated levels of IL-6.
The objectivation of high interleukin 6 levels in these patients should be an important scientific argument to justify the administration of therapy based on antagonization of IL6. Measurement of other pro inflammatory cytokines will shed light on the mechanism of the inflammatory syndrome induced by the SARS-CoV-2 virus.
One of the pathophysiological mechanisms of pulmonary pathology could be the induction of the production of complement factors by interleukin 6 as well as the activation of the complement cascade by the virus via the lectin pathway. It is known that one of the effects of Tocilizumab is to reduce the concentration of the various complement factors, the synthesis of which is under the control of interleukin 6. This is why this study proposes to measure certain parameters of the complement (CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2) in order to objectify and quantify this activation.
If the activation of the complement proves significant it could be an argument for a treatment targeting more specifically the cascade of the complement.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ventilation support | Experimental | Diagnostic Test: Cytokines dosage, Diagnostic Test: Complement dosageThe experimental group will include Covid-19 infected patients with non-invasive or invasive ventilation support (BCRSS score ≥3). |
| Control group | Other | Diagnostic Test: Cytokines dosage, Diagnostic Test: Complement dosageThe control group will include Covid-19 infected patients who don't have respiratory problems justifying a transfer to intensive care. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytokines dosageDosage 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...). | Diagnostic test | Control group, Ventilation support |
| Complement dosageDosage of the complement parameters: CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2. | Diagnostic test | Control group, Ventilation support |
Primary outcome
IL6 concentration
Time frame: Before anti-IL6R treatment (baseline)
Interleukine 6, soluble IL6-R, complex IL6-IL6R concentration
IL6 concentration change from baseline value
Time frame: Twice a week from day 1 to day 14 post anti-IL6R administration
Interleukine 6 soluble IL6-R, complex IL6-IL6R variation compared to baseline value
Complement parameters
Time frame: Before anti-IL6R treatment (baseline)
CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2
Complement parameters change from baseline values
Time frame: Twice a week from day 1 to day 14 post anti-IL6R administration
CH50, C3, C4, C3d, C5a, SC5b-9, C4a, MASP-2 variation compared to baseline values
Inflammatory cytokines baseline concentrations
Time frame: Before anti-IL6R treatment (baseline)
Concentration of TNFa, IFNg, IL1, IL7, IL10, IL12, IL17, IL18
Inflammatory cytokines change from baseline values
Time frame: Twice a week from day 1 to day 14 post anti-IL6R administration
Concentration of TNFa, IFNg, IL1, IL7, IL10, IL12, IL17, IL18 variation compared to baseline values
2 secondary outcomes
Concentration of markers of macrophage activation
Time frame: Before anti-IL6R treatment (baseline)
Markers of macrophage activation change from baseline values
Time frame: Twice a week from day 1 to day 14 post anti-IL6R administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Derived from this study: PubMed 35085462Ponthieux 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytokines dosage and Complement dosage in people with COVID-19, run by Francis Corazza at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IL6 concentration (time frame: Before anti-IL6R treatment (baseline)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04346017, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2021.