Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Belgium Health Care Knowledge Centre | OTHER_GOV |
Not provided
Not provided
Not provided
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
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Usual Care | Placebo Comparator |
| |
| Anakinra | Active Comparator |
| |
| Siltuximab | Active Comparator |
| |
| Anakinra + Siltuximab | Active Comparator |
| |
| Tocilizumab | Active Comparator |
| |
| Anakinra + Tocilizumab | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Usual Care | Other | Usual Care |
| |
| Anakinra |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | at day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Time Untill Discharge | during hospital admission (up to 28 days) | |
| Time Until Independence From Supplemental Oxygen or Discharge | during hospital admission (up to 28 days) | |
Not provided
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:
serum ferritin concentration >1000 mcg/L and rising since last 24h
single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation
lymphopenia defined as <800 lymphocytes/microliter) and two of the following extra criteria
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:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Bart Lambrecht, MD, PhD | University Hospital, Ghent | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AZ Sint-Jan Brugge | Bruges | 8000 | Belgium | |||
| University Hospital Saint-Pierre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35080773 | Derived | 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. | |
| 34756178 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
111 received siltuximab at day 1, 2 received no siltuximab due to withdrawal of consent. 113 received tocilizumab at day 1, 1 was not administered for unknown reason.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Usual Care | Usual Care: Usual Care |
| FG001 | Anakinra: IL1-blocker | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first |
| FG002 | Siltuximab: IL-6 Blocker | Siltuximab: Siltuximab will be given via single IV infusion at a dose of 11 mg/kg |
| FG003 | Anakinra + Siltuximab | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first Siltuximab: Siltuximab will be given via single IV infusion at a dose of 11 mg/kg |
| FG004 | Tocilizumab: IL-6 Blocker | Tocilizumab: Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection |
| FG005 | Anakinra + Tocilizumab | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first Tocilizumab: Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Blockade | Patients receiving Anakinra, patients receiving Siltuximab, patients receiving Tocilizumab, patients receiving Anakinra and Siltuximab, patients receiving Anakinra and Tocilizumab |
| BG001 | No Blockade |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | at day 15 |
|
AE's are recorded from randomisation until the end of the study, 5 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Usual Care | Usual Care: Usual Care | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arterial thromboembolism | Vascular disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anja Delporte | UZ Gent | +3293320228 | anja.delporte@uzgent.be |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 3, 2020 | Sep 13, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 5, 2021 | Sep 13, 2022 | SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D055371 | Acute Lung Injury |
| D000860 | Hypoxia |
| D012128 | Respiratory Distress Syndrome |
| D045169 | Severe Acute Respiratory Syndrome |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D053590 | Interleukin 1 Receptor Antagonist Protein |
| C504234 | siltuximab |
| C502936 | tocilizumab |
| ID | Term |
|---|---|
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first |
|
|
| Siltuximab | Drug | Siltuximab will be given via single IV infusion at a dose of 11 mg/kg |
|
|
| Tocilizumab | Drug | Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection |
|
|
| Time Until Independence From Invasive Ventilation |
| during hospital admission (up to 54 days) |
| Number of Days in ICU | during hospital admission (up to 28 days) |
| Number of Days in ICU in Patients Ventilated at Day of Randomization | during hospital admission (up to 28 days) |
| Number of Days Without Supplemental Oxygen Use | during hospital admission (up to 28 days) |
| Number of Invasive Ventilator Days | during hospital admission (up to 28 days) |
| Number of Invasive Ventilator Days in Patients Ventilated at Day of Randomization | during hospital admission (up to 28 days) |
| Number of Invasive Ventilator-free Days | during hospital admission (up to 28 days) |
| Number of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization | during hospital admission (up to 28 days) |
| 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). | first 28 days after randomization |
| 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). | the first 28 days after randomization |
| Time Until First Use of High-flow Oxygen Device, Ventilation, or Death | during hospital admission (up to 28 days) |
| 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 | Ghent | 9000 | Belgium |
| University Hospital Ghent | Ghent | 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 |
| Derived |
| 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. |
| 33935163 | Derived | 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. |
| 32493441 | Derived | 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. |
| Other |
|
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
Participants receiving no IL1 blockade + participants receiving no IL6 blockade
| BG002 | Total | Total of all reporting groups |
| Median |
| Inter-Quartile Range |
| years |
|
| Sex/Gender, Customized | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| Body Mass Index (BMI) | BMI was available for 108 of 112 participants that received the IL-1 Blockade, for 222 of 227 participants that received the IL-6 Blockade, for 222 of 230 that received no IL-1 blockade, and for 108 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | kg/m^2 |
|
| Smoking | Smoking status was available for 95 of 112 participants that received the IL-1 Blockade, 181 of 227 participants that received the IL-6 Blockade, 186 of 230 participants that received no IL-1 blockade, and for 100 of 115 participants that received no IL-6 blockade | Count of Participants | Participants |
|
| Co-existing conditions | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| 6-category ordinal scale for clinical improvement at day of randomization | 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 | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| ICU at day of randomization | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| SOFA score at day of randomization | The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points. | SOFA score was available for 109 of 112 participants that received the IL-1 Blockade , for 208 of 227 that received the IL-6 Blockade, for 207 of 230 that received no IL-1 blockade, and for 108 of 115 that received no IL-6 blockade | Median | Inter-Quartile Range | units on a scale |
|
| PaO2/FiO2 ratio at day of randomization | PaO2/FiO2 ratio is the ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2; PaO2/FiO2). | PaO2/FiO2 was available for 99 of 112 participants that received the IL-1 Blockade, for 216 of 227 participants that received the IL-6 Blockade, for 228 of 230 that received no IL-1 blockade, and for 111 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | ratio |
|
| Vasopressor use at day of randomization | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| Days of symptoms at randomization | Days of symptoms at randomization was available for 100 of 112 participants that received the IL-1 Blockade, for 214 of 227 participants that received the IL-6 Blockade, for 207 of 230 participants that received no IL-1 blockade, and for 107 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | days |
|
| days of hospitalization at randomization | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Median | Inter-Quartile Range | days |
|
| Concommitant medication at day of randomization | 112 participants received the IL-1 Blockade, 227 received the IL-6 Blockade, 230 received no IL-1 blockade, and 115 received no IL-6 blockade | Count of Participants | Participants |
|
| CRP at day of randomization | CRP was available for all 112 participants that received the IL-1 Blockade, for 226 of 227 participants that received the IL-6 Blockade, for 224 of 230 that received no IL-1 blockade, and for 114 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | mg/mL |
|
| Lymphocyte count at day of randomization | Lymphocyte count at day of randomization was available for 108 of 112 participants that received the IL-1 Blockade, for 220 of 227 participants that received the IL-6 Blockade, for 224 of 230 that received no IL-1 blockade, and for 112 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | 10^3 cells /µL |
|
| Ferritin at day of randomization | Ferritin at day of randomization was available for 109 of 112 participants that received the IL-1 Blockade, for 222 of 227 participants that received the IL-6 Blockade, for 223 of 230 that received no IL-1 blockade, and for 110 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | µg/L |
|
| D-dimers at day of randomization | D-dimers at day of randomization was available for 90 of 112 participants that received the IL-1 Blockade, for 192 of 227 participants that received the IL-6 Blockade, for 193 of 230 that received no IL-1 blockade, and for 91 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | ng/mL |
|
| LDH at day of randomization | LDH was available for 111 of 112 participants that received the IL-1 Blockade, for 224 of 227 participants that received the IL-6 Blockade, for 224 of 230 that received no IL-1 blockade, and for 111 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | IU/L |
|
| IL-1-RA at day of randomization | IL-1-RA at day of randomization was available for 108 of 112 participants that received the IL-1 Blockade, for 216 of 227 participants that received the IL-6 Blockade, for 216 of 230 that received no IL-1 blockade, and for 108 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | ng/mL |
|
| IL-1B at day of randomization | IL-1B at day of randomization was available for 104 of 112 participants that received the IL-1 Blockade, for 213 of 227 participants that received the IL-6 Blockade, for 210 of 230 that received no IL-1 blockade, and for 107 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | fg/mL |
|
| IL-6 at day of randomization | IL-6 at day of randomization was available for 108 of 112 participants that received the IL-1 Blockade, for 216 of 227 participants that received the IL-6 Blockade, for 216 of 230 that received no IL-1 blockade, and for 108 of 115 participants that received no IL-6 blockade | Median | Inter-Quartile Range | pg/mL |
|
| OG001 | No IL-1 Blockade | Some patients received IL-6 blockade with Sylvant® (Siltuximab) single IV infusion from 100mg powder concentrate and 400mg powder concentrate, OR Roactemra® (tocilizumab) IV- Infusion prepared starting from flasks containing 400mg/20ml stock solution (to dilute for infusion) or from Prefilled syringe 162mg / 0.9ml SC |
| OG002 | IL-6 Blockade | Patients received either Sylvant® (Siltuximab) single IV infusion from 100mg powder concentrate and 400mg powder concentrate, OR Roactemra® (tocilizumab) IV- Infusion prepared starting from flasks containing 400mg/20ml stock solution (to dilute for infusion) or from Prefilled syringe 162mg / 0.9ml SC Some patients also received Kineret® (Anakinra) 100mg pre-filled syringe given 1x / day for 28 days (or until discharge from hospital) |
| OG003 | No IL-6 Blockade | Some patients received Kineret® (Anakinra) 100mg pre-filled syringe given 1x / day for 28 days (or until discharge from hospital) |
|
|
| Secondary | Time Untill Discharge | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Time Until Independence From Supplemental Oxygen or Discharge | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Time Until Independence From Invasive Ventilation | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 54 days) |
|
|
|
| Secondary | Number of Days in ICU | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Days in ICU in Patients Ventilated at Day of Randomization | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Days Without Supplemental Oxygen Use | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Invasive Ventilator Days | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Invasive Ventilator Days in Patients Ventilated at Day of Randomization | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Invasive Ventilator-free Days | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Invasive Ventilator-free Days in Patients Ventilated at Day of Randomization | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| Secondary | 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). | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | percentage of days | first 28 days after randomization |
|
|
|
| Secondary | 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). | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | percentage of days | the first 28 days after randomization |
|
|
|
| Secondary | Time Until First Use of High-flow Oxygen Device, Ventilation, or Death | Participants were re-grouped and analyzed based on the following pre-specified factorial combinations: IL-1 Blockade, No IL-1 Blockade, IL-6 Blockade, No IL-6 Blockade | Posted | Median | 95% Confidence Interval | days | during hospital admission (up to 28 days) |
|
|
|
| 74 |
| 14 |
| 74 |
| 37 |
| 74 |
| EG001 | Anakinra | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first | 10 | 44 | 12 | 44 | 25 | 44 |
| EG002 | Siltuximab | Siltuximab: Siltuximab will be given via single IV infusion at a dose of 11 mg/kg | 15 | 75 | 21 | 75 | 15 | 75 |
| EG003 | Anakinra + Siltuximab | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first Siltuximab: Siltuximab will be given via single IV infusion at a dose of 11 mg/kg | 6 | 36 | 8 | 36 | 17 | 36 |
| EG004 | Tocilizumab | Tocilizumab: Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection | 10 | 81 | 15 | 81 | 35 | 81 |
| EG005 | Anakinra + Tocilizumab | Anakinra: Anakinra will be given as a daily subcutaneous injection of 100 mg for 28 days or until hospital discharge, whichever is first Tocilizumab: Tocilizumab will be given via single IV infusion at a dose of 8 mg/kg with a maximum infusion of 800 mg/injection | 5 | 32 | 9 | 32 | 17 | 32 |
| Thromboembolic event | Vascular disorders | Non-systematic Assessment |
|
| Other | Surgical and medical procedures | Non-systematic Assessment |
|
| Anaphylaxis | Immune system disorders | Non-systematic Assessment |
|
| Disease progression | General disorders | Non-systematic Assessment |
|
| Multi-organ failure | General disorders | Non-systematic Assessment |
|
| postoperative haemorrhage | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | Non-systematic Assessment |
|
| Asystole | Cardiac disorders | Non-systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | Non-systematic Assessment |
|
| Other | Cardiac disorders | Non-systematic Assessment |
|
| Mitral valve disease | Cardiac disorders | Non-systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Laryngeal stenosis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Other | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Edema cerebral | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | Non-systematic Assessment |
|
| Intracranial haemorrhage | Nervous system disorders | Non-systematic Assessment |
|
| Stroke | Nervous system disorders | Non-systematic Assessment |
|
| Gastric haemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
|
| Jejunal haemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
|
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | Non-systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hepatic infection | Infections and infestations | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | Non-systematic Assessment |
|
| Thromboembolic event | Vascular disorders | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | Non-systematic Assessment |
|
| Creatinine increased | Investigations | Non-systematic Assessment |
|
| GGT increased | Investigations | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Other | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Other | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Delirium | Psychiatric disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Diarrhoea | Psychiatric disorders | Non-systematic Assessment |
|
| Gastroparesis | Psychiatric disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
|
| Other | Renal and urinary disorders | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | lower limb |
|
| Hyperglycaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Other | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
|
Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D055370 | Lung Injury |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |
| D011506 | Proteins |
| D001685 | Biological Factors |