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CompletedNCT04330638COV-AIDUpdated Mar 14, 2023Results posted

Treatment of COVID-19 Patients With Anti-interleukin Drugs

A Phase 3 interventional study of Usual Care and Anakinra in COVID-19, sponsored by University Hospital, Ghent. Completed at 15 sites in Belgium. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-14.

Sponsored by University Hospital, Ghent · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
342
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6 and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome

Read the detailed description

There are currently no treatments directed at halting the cytokine storm and acute lung injury to stop the progression from manageable hypoxia to frank respiratory failure and ARDS in patients with COVID-19 infection. Preventing progression from early acute hypoxia and cytokine release syndrome to frank hypoxic respiratory failure and ARDS could have a huge impact on the foreseeable overflow of the ICU units. In ventilated patients, preventing the onset of ARDS, or shortening ICU stay could also be crucial in this regard.

The clinical status after 15 days treatment is evaluated to measure the effectiveness of tocilizumab, tocilizumab and anakinra, siltuximab, siltuximab and anakinra and anakinra on restoring lung homeostasis,using single IV injection (siltuximab or tocilizumab) combined or not with daily subcutaneous injections of anakinra until 28 days or hospital discharge, whichever is first. During the treatment period, daily clinical assesments of severity, daily laboratory check-up, measurements of oxygen saturation (pulse oximetry) in relation to FiO2, regular arterial blood gas measurements, regular chest X-rays, chest CT scans on indication will be performed.

02

Conditions studied

  • COVID-19

Keywords

  • Acute Lung Injury
  • Hypoxia
  • Acute Respiratory Distress Syndrome
  • Corona virus
  • COVID-19
  • SARS (Severe Acute Respiratory Syndrome)
  • Systemic Cytokine release Syndrome
03

In context

COVID-19

7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.

This study's enrollment of 342 is above the median of 100 across 4,099 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

University Hospital, Ghent is the lead sponsor of 665 studies on the registry; 156 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Recent ( ≥ 6 days of flu-like symptoms or malaise yet ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
  • Confident COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period.
  • In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (\<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.
  • Presence of hypoxia defined as PaO2/FiO2 below 350 while breathing room air in upright position or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation

  • signs of cytokine release syndrome defined as ANY of the following:

    1. serum ferritin concentration >1000 mcg/L and rising since last 24h
    2. single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation

    3. lymphopenia defined as \<800 lymphocytes/microliter) and two of the following extra criteria

      • Ferritin > 700 mcg/L and rising since last 24h
      • increased LDH (above 300 IU/L) and rising last 24h
      • D-Dimers > 1000 ng/mL and rising since last 24h
      • CRP above 70mg/L and rising since last 24h and absence of bacterial infection
      • if three of the above are present at admission, no need to document 24h rise
  • Chest X-ray or CT scan showing bilateral infiltrates within last 2 days
  • Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients
  • Age ≥ 18yrs
  • Male or Female
  • Willing and able to provide informed consent or legal representative willing to provide informed consent

Exclusion criteria

Exclusion Criteria:

  • Patients with known history of serious allergic reactions, including anaphylaxis, to any of the study medications, or any component of the product.
  • mechanical ventilation > 24 h at Randomization
  • Patient on ECMO at time of screening
  • clinical frailty scale above 3 (This frailty score is the patient status before first symptoms of COVID-19 episode.)
  • active bacterial or fungal infection
  • unlikely to survive beyond 48h
  • neutrophil count below 1500 cells/microliter
  • platelets below 50.000/microliter
  • Patients enrolled in another investigational drug study
  • patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder
  • patients on immunosuppressant or immunomodulatory drugs
  • patients on current anti-IL1 or anti-IL6 treatment
  • signs of active tuberculosis
  • serum transaminase levels >5 times upper limit of normal
  • bowel perforation or diverticulitis
  • pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)
  • Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Woùmen of childbearing potential must consistently and correctly use (during the entire treatment period and 3 months after last reatment) 1 highly effective method for contraception.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
None (open label)
Enrollment
342 participants (actual)

Study arms

  • Placebo comparator
    Usual Care

    Other: Usual Care

  • Active comparator
    Anakinra

    Drug: Anakinra

  • Active comparator
    Siltuximab

    Drug: Siltuximab

  • Active comparator
    Anakinra + Siltuximab

    Drug: Anakinra · Drug: Siltuximab

  • Active comparator
    Tocilizumab

    Drug: Tocilizumab

  • Active comparator
    Anakinra + Tocilizumab

    Drug: Anakinra · Drug: Tocilizumab

Interventions

  • OtherUsual Care

    Usual Care

  • DrugAnakinra

    Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first

    Also known as: KINERET®

  • DrugSiltuximab

    Siltuximab will be given via single IV infusion at a dose of 11 mg/kg

    Also known as: SYLVANT®

  • DrugTocilizumab

    Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection

    Also known as: ROACTEMRA®

06

What researchers measure

Primary outcomes

  1. Time to Clinical Improvement

    Time to Clinical Improvement is defined as the time from randomization to either an increase of at least two points on a six category ordinal scale from the status at randomization or live discharge from the hospital.The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome

    Time frame: at day 15

Secondary outcomes

  1. Time Untill Discharge

    Time frame: during hospital admission (up to 28 days)

  2. Time Until Independence From Supplemental Oxygen or Discharge

    Time frame: during hospital admission (up to 28 days)

  3. Time Until Independence From Invasive Ventilation

    Time frame: during hospital admission (up to 54 days)

  4. Number of Days in ICU

    Time frame: during hospital admission (up to 28 days)

  5. Number of Days in ICU in Patients Ventilated at Day of Randomization

    Time frame: during hospital admission (up to 28 days)

  6. Number of Days Without Supplemental Oxygen Use

    Time frame: during hospital admission (up to 28 days)

  7. Number of Invasive Ventilator Days

    Time frame: during hospital admission (up to 28 days)

  8. Number of Invasive Ventilator Days in Patients Ventilated at Day of Randomization

    Time frame: during hospital admission (up to 28 days)

  9. Number of Invasive Ventilator-free Days

    Time frame: during hospital admission (up to 28 days)

  10. Number of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization

    Time frame: during hospital admission (up to 28 days)

  11. Percentage of Days in ICU

    Number of days the participants were ventilated, relative to the number of days participants were alive during the first 28 days after randomization. This was calculated as the number of days with need for invasive ventilation / number of days alive during first 28 days, multiplied by 100 (to obtain a percentage).

    Time frame: first 28 days after randomization

  12. Percentage of Invasive Ventilator Days

    Number of days the participant spent in the ICU, relative to the number of days the patient was alive during the first 28 days after randomization. This was calculated as the number of days in ICU during first 28 days / number of days alive during first 28 days, multiplied by 100 (to obtain a percentage).

    Time frame: the first 28 days after randomization

  13. Time Until First Use of High-flow Oxygen Device, Ventilation, or Death

    Time frame: during hospital admission (up to 28 days)

07

Results

Posted Mar 14, 2023

Participant flow

Between April 4th and December 6th, 2020, 342 patients were randomized. In the first randomization, 230 patients were assigned to the no IL-1 blockade group and 112 to the IL-1 blockade group, of which all received at least one dose of anakinra. In the second randomization, 115 patients were assigned to the no IL-6 blockade group, and 227 to the IL-6 blockade group, of which 114 were allocated to receive tocilizumab and 113 siltuximab.

Participant flow — Overall Study
MilestoneUsual CareAnakinra: IL1-blockerSiltuximab: IL-6 BlockerAnakinra + SiltuximabTocilizumab: IL-6 BlockerAnakinra + Tocilizumab
Started744475368132
Randomization 1: no il-1 blockade740750810
Randomization 1: il-1 blockade044036032
Randomization 2: no il-6 blockade74410000
Randomization 2: il-6 blockade0075368132
Completed563052276525
Not completed1814239167
Withdrew: Adverse event910156105
Withdrew: Other225132
Withdrew: Withdrawal by subject400000
Withdrew: Lost to follow-up323230

Outcome measures

PrimaryTime to Clinical Improvement

Time to Clinical Improvement is defined as the time from randomization to either an increase of at least two points on a six category ordinal scale from the status at randomization or live discharge from the hospital.The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome

Time frame:
at day 15
Reported as:
Median · days
Time to Clinical Improvement
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Time to Clinical Improvement12 (10 to 16)12 (10 to 15)11 (10 to 16)12 (11 to 16)
SecondaryTime Untill Discharge
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Time Untill Discharge
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Time Untill Discharge14 (11 to 19)12 (11 to 18)12 (11 to 18)13 (11 to 19)
SecondaryTime Until Independence From Supplemental Oxygen or Discharge
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Time Until Independence From Supplemental Oxygen or Discharge
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Time Until Independence From Supplemental Oxygen or Discharge12 (10 to 20)12 (10 to 15)11 (10 to 15)12 (10 to 15)
SecondaryTime Until Independence From Invasive Ventilation
Time frame:
during hospital admission (up to 54 days)
Reported as:
Median · days
Time Until Independence From Invasive Ventilation
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Time Until Independence From Invasive Ventilation21 (8 to NA)27 (9 to NA)23 (8 to NA)54 (9 to NA)
SecondaryNumber of Days in ICU
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Days in ICU
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Days in ICU11 (8 to 15)10 (8 to 13)11 (8 to 14)10 (7 to 15)
SecondaryNumber of Days in ICU in Patients Ventilated at Day of Randomization
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Days in ICU in Patients Ventilated at Day of Randomization
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Days in ICU in Patients Ventilated at Day of Randomization20 (15 to 27)22 (17 to 29)20 (16 to 27)22 (16 to 29)
SecondaryNumber of Days Without Supplemental Oxygen Use
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Days Without Supplemental Oxygen Use
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Days Without Supplemental Oxygen Use9 (7 to 12)9 (7 to 11)10 (8 to 12)8 (6 to 11)
SecondaryNumber of Invasive Ventilator Days
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Invasive Ventilator Days
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Invasive Ventilator Days5 (3 to 9)5 (3 to 7)5 (3 to 7)5 (3 to 9)
SecondaryNumber of Invasive Ventilator Days in Patients Ventilated at Day of Randomization
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Invasive Ventilator Days in Patients Ventilated at Day of Randomization
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Invasive Ventilator Days in Patients Ventilated at Day of Randomization15 (11 to 20)16 (13 to 21)15 (12 to 20)16 (12 to 22)
SecondaryNumber of Invasive Ventilator-free Days
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Invasive Ventilator-free Days
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Invasive Ventilator-free Days18 (15 to 21)18 (16 to 20)18 (17 to 20)17 (15 to 20)
SecondaryNumber of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Number of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Number of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization6 (3 to 14)6 (3 to 13)7 (4 to 15)5 (2 to 12)
SecondaryPercentage of Days in ICU

Number of days the participants were ventilated, relative to the number of days participants were alive during the first 28 days after randomization. This was calculated as the number of days with need for invasive ventilation / number of days alive during first 28 days, multiplied by 100 (to obtain a percentage).

Time frame:
first 28 days after randomization
Reported as:
Median · percentage of days
Percentage of Days in ICU
percentage of daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Percentage of Days in ICU42 (31 to 56)36 (29 to 46)38 (30 to 48)40 (29 to 54)
SecondaryPercentage of Invasive Ventilator Days

Number of days the participant spent in the ICU, relative to the number of days the patient was alive during the first 28 days after randomization. This was calculated as the number of days in ICU during first 28 days / number of days alive during first 28 days, multiplied by 100 (to obtain a percentage).

Time frame:
the first 28 days after randomization
Reported as:
Median · percentage of days
Percentage of Invasive Ventilator Days
percentage of daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Percentage of Invasive Ventilator Days23 (14 to 38)21 (14 to 31)21 (14 to 30)23 (14 to 38)
SecondaryTime Until First Use of High-flow Oxygen Device, Ventilation, or Death
Time frame:
during hospital admission (up to 28 days)
Reported as:
Median · days
Time Until First Use of High-flow Oxygen Device, Ventilation, or Death
daysIL 1 BlockadeNo IL-1 BlockadeIL-6 BlockadeNo IL-6 Blockade
Time Until First Use of High-flow Oxygen Device, Ventilation, or DeathNA (NA to NA)NA (NA to NA)NA (NA to NA)NA (NA to NA)

Adverse events

Collected over AE's are recorded from randomisation until the end of the study, 5 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Usual Care9/74 (12.2%)14/74 (18.9%)37/74 (50%)
Anakinra10/44 (22.7%)12/44 (27.3%)25/44 (56.8%)
Siltuximab15/75 (20%)21/75 (28%)15/75 (20%)
Anakinra + Siltuximab6/36 (16.7%)8/36 (22.2%)17/36 (47.2%)
Tocilizumab10/81 (12.3%)15/81 (18.5%)35/81 (43.2%)
Anakinra + Tocilizumab5/32 (15.6%)9/32 (28.1%)17/32 (53.1%)
Most frequent serious events
Showing 10 of 36
Most frequent serious events
EventUsual CareAnakinraSiltuximabAnakinra + SiltuximabTocilizumabAnakinra + Tocilizumab
Arterial thromboembolismVascular disorders0/740/4421/751/360/810/32
Respiratory failureRespiratory, thoracic and mediastinal disorders2/745/449/752/366/811/32
SepsisInfections and infestations3/745/446/753/362/812/32
Lung infectionInfections and infestations0/741/440/750/360/812/32
Multi-organ failureGeneral disorders3/742/440/750/362/811/32
AspirationRespiratory, thoracic and mediastinal disorders0/740/440/750/360/811/32
Laryngeal stenosisRespiratory, thoracic and mediastinal disorders0/740/440/750/360/811/32
PneumothoraxRespiratory, thoracic and mediastinal disorders0/740/442/750/361/811/32
StrokeNervous system disorders0/740/441/750/361/811/32
Lower gastrointestinal haemorrhageGastrointestinal disorders0/740/440/750/360/811/32
Most frequent other events
Showing 10 of 34
Most frequent other events
EventUsual CareAnakinraSiltuximabAnakinra + SiltuximabTocilizumabAnakinra + Tocilizumab
ConstipationGastrointestinal disorders10/745/449/754/368/817/32
Lung infectionInfections and infestations7/744/448/753/368/815/32
OtherRespiratory, thoracic and mediastinal disorders0/745/442/750/361/810/32
OtherBlood and lymphatic system disorders0/743/444/754/363/810/32
Sinus bradycardiaCardiac disorders1/740/448/752/362/810/32
HypertensionVascular disorders4/743/444/751/363/813/32
Atrial fibrillationCardiac disorders3/740/447/751/360/813/32
HyperglycaemiaMetabolism and nutrition disorders2/740/444/751/362/813/32
HypertriglyceridaemiaMetabolism and nutrition disorders1/742/443/752/361/813/32
Alanine aminotransferase increasedInvestigations3/743/447/753/367/811/32

Baseline characteristics

The study investigates IL-6 and IL-1 blockade 339 participants received IL Blockade: 227 participants IL-6 blockade + 112 participants IL-1 blockade; 345 participants No Blockade: 230 participants no IL-6 blockade + 115 participants no IL-1 blockade

Age, Continuous
Age, Continuous(years)BlockadeNo BlockadeTotal
IL-167 (56 to 74)64 (54 to 72)65 (54 to 73)
IL-665 (54 to 73)64 (55 to 72)65 (54 to 73)
Sex/Gender, Customized
Sex/Gender, Customized(Participants)BlockadeNo BlockadeTotal
IL-1: Female255277
IL-1: Male87178265
IL-6: Female522577
IL-6: Male17590265
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)BlockadeNo BlockadeTotal
IL-1 : white98180278
IL-1: Middle Eastern-Arabian112940
IL-1:Black189
IL-1: Asian167
IL-1 : Other178
IL-6 : white18494278
IL-6 : Middle Eastern-Arabian271340
IL-6: Black819
IL-6: Asian437
IL-6: Other448
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)BlockadeNo BlockadeTotal
IL-128 (26 to 32)28 (26 to 32)28 (26 to 32)
IL-628 (26 to 33)28 (26 to 31)28 (26 to 32)
Smoking
Smoking(Participants)BlockadeNo BlockadeTotal
IL-1:No54108162
IL-1: Current71118
IL-1: Former3467101
IL-6: No10161162
IL-6: Current15318
IL-6: Former6536101
Co-existing conditions
Co-existing conditions(Participants)BlockadeNo BlockadeTotal
IL-1: Arterial hypertension57104161
IL-1 Diabetes mellitus375895
IL-1: Cardiovascular disease294170
IL-1: Chronic kidney disease142337
IL-6: Arterial hypertension11546161
IL-6 Diabetes mellitus593695
IL-6: Cardiovascular disease462470
IL-6: Chronic kidney disease251237
6-category ordinal scale for clinical improvement at day of randomization
6-category ordinal scale for clinical improvement at day of randomization(Participants)BlockadeNo BlockadeTotal
IL-1: Hospitalized, on invasive mechanical ventilation (2)142236
IL-1: Hospitalized, on non-invasive ventilation or high flow oxygen devices (3)4484128
IL-1: Hospitalized, requiring supplemental oxygen (4)50119169
IL-1: Hospitalized, not requiring supplemental oxygen (5)156
IL-6: Hospitalized, on invasive mechanical ventilation (2)221739
IL-6: Hospitalized, on non-invasive ventilation or high flow oxygen devices (3)8939128
IL-6: Hospitalized, requiring supplemental oxygen (4)11158169
IL-6: Hospitalized, not requiring supplemental oxygen (5)516
ICU at day of randomization
ICU at day of randomization(Participants)BlockadeNo BlockadeTotal
IL-160112172
IL-611359172

14 further baseline measures are reported on the registry.

08

Study locations

15 sites
  • AZ Sint-Jan Brugge
    Brugge, 8000, Belgium
  • University Hospital Saint-Pierre
    Brussels, 1000, Belgium
  • Erasmus University Hospital
    Brussels, 1070, Belgium
  • University Hospital Saint-Luc
    Brussels, 1200, Belgium
  • University Hospital Antwerp
    Edegem, 2650, Belgium
  • Ziekenhuis Oost-Limurg
    Genk, 3600, Belgium
  • AZ Sint-Lucas
    Gent, 9000, Belgium
  • University Hospital Ghent
    Gent, 9000, Belgium
  • Jessa ZH
    Hasselt, 3500, Belgium
  • University Hospital Brussels
    Jette, 1090, Belgium
  • CHU Tivoli
    La Louvière, 7100, Belgium
  • CHR de la Citadelle
    Liège, 4000, Belgium
  • University Hospital Liège
    Liège, 4000, Belgium
  • Cliniques Saint-Pierre Ottignies
    Ottignies-Louvain-la-Neuve, 1340, Belgium
  • AZ Delta
    Roeselare, 8800, Belgium
09

References and documents

Publications

  • Davidson M, Menon S, Chaimani A, Evrenoglou T, Ghosn L, Grana C, Henschke N, Cogo E, Villanueva G, Ferrand G, Riveros C, Bonnet H, Kapp P, Moran C, Devane D, Meerpohl JJ, Rada G, Hrobjartsson A, Grasselli G, Tovey D, Ravaud P, Boutron I. Interleukin-1 blocking agents for treating COVID-19. Cochrane Database Syst Rev. 2022 Jan 26;1(1):CD015308. doi: 10.1002/14651858.CD015308. PubMed 35080773 ↗
  • Declercq J, Van Damme KFA, De Leeuw E, Maes B, Bosteels C, Tavernier SJ, De Buyser S, Colman R, Hites M, Verschelden G, Fivez T, Moerman F, Demedts IK, Dauby N, De Schryver N, Govaerts E, Vandecasteele SJ, Van Laethem J, Anguille S, van der Hilst J, Misset B, Slabbynck H, Wittebole X, Lienart F, Legrand C, Buyse M, Stevens D, Bauters F, Seys LJM, Aegerter H, Smole U, Bosteels V, Hoste L, Naesens L, Haerynck F, Vandekerckhove L, Depuydt P, van Braeckel E, Rottey S, Peene I, Van Der Straeten C, Hulstaert F, Lambrecht BN. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial. Lancet Respir Med. 2021 Dec;9(12):1427-1438. doi: 10.1016/S2213-2600(21)00377-5. Epub 2021 Oct 29. PubMed 34756178 ↗
  • Brands X, de Vries FMC, Uhel F, Haak BW, Peters-Sengers H, Schuurman AR, van Engelen TSR, Lutter R, Cremer OL, Bonten MJ, Schultz MJ, Scicluna BP, van der Poll T; MARS Consortium. Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia. Crit Care Med. 2021 Nov 1;49(11):1901-1911. doi: 10.1097/CCM.0000000000005072. PubMed 33935163 ↗
  • Maes B, Bosteels C, De Leeuw E, Declercq J, Van Damme K, Delporte A, Demeyere B, Vermeersch S, Vuylsteke M, Willaert J, Bolle L, Vanbiervliet Y, Decuypere J, Libeer F, Vandecasteele S, Peene I, Lambrecht B. Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 3;21(1):468. doi: 10.1186/s13063-020-04453-5. Erratum In: Trials. 2020 Jun 22;21(1):556. doi: 10.1186/s13063-020-04519-4. PubMed 32493441 ↗

Study documents

  • Study protocol · Nov 3, 2020
  • Statistical analysis plan · Mar 5, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 14, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04330638
Lead sponsor
University Hospital, Ghent
Collaborators
Belgium Health Care Knowledge Centre
Responsible party
Bart N. Lambrecht (Professor in Pulmonology, Director VIB-Inflammational Research Center, University Hospital, Ghent) — Principal investigator
First posted
Apr 1, 2020
Start date
Apr 3, 2020
Primary completion
Dec 20, 2020
Completion
May 21, 2021
Results posted
Mar 14, 2023
Last update
Mar 14, 2023

Study contacts

Bart Lambrecht, MD, PhD
principal investigator · University Hospital, Ghent

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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