• Known severe allergic reactions to tocilizumab or other monoclonal antibodies
• Active tuberculosis infection based on history
• Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Have received oral anti-rejection or immunomodulatory drugs (including tocilizumab) with the past 6 months
• Participating in other drug clinical trials (participation in COVID-19 trials allowed)
• Self-reported pregnant or breastfeeding
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at baseline
• Absolute neutrophil count (ANC) < 1000/mL at baseline
• Platelet count < 50,000/mL at baseline

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Known severe allergic reactions to monoclonal antibodies
• Active confirmed tuberculosis with ongoing treatment or obvious tuberculosis or obvious other bacterial, fungal or viral infection (besides COVID-19)
• In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Long-term oral anti-rejection or immunomodulatory drugs (including corticosteroids equivalent to methylprednison 15mg/day)
• Pregnant or lactating women. If needed, exclusion of pregnancy should be performed by laboratory test (U-hCG-O)
• Participating in other drug clinical trials
• Absolute neutrophil count < 1 x10E9/l
• Platelet count <50 x10E9/l
• ALAT >10x ULN

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Concurrent use of invasive mechanical ventilation
• Concurrent use of vasopressor or inotropic medications
• Previous receipt of tocilizumab or another anti-IL6R or IL-6 inhibitor in the year prior
• Known history of hypersensitivity to tocilizumab
• Diagnosis of end-stage liver disease or listed for liver transplant
• Elevation of AST or ALT in excess of 10 times the upper limit of normal
• Neutropenia (Absolute neutrophil count < 500/uL)
• Thrombocytopenia (Platelets < 50,000/uL)
• On active therapy with a Bruton's tyrosine kinase-targeted agent, which include the following: Acalabrutinib, Ibrutinib, Zanubrutinib
• On active therapy with a JAK2-targeted agent, which include the following:Tofacitinib, Baricitinib, Upadacitinib, Ruxolitinib
• Any of the following biologic immunosuppressive agent (and any biosimilar versions thereof) administered in the past 6 months or less: Abatacept, Adalimumab, Alemtuzumab, Atezolizumab, Belimumab, Blinatumomab, Brentuximab, Certolizumab, Daratumumab, Durvalumab, Eculizumab, Elotuzumab, Etanercept, Gemtuzumab, Golimumab, Ibritumomab, Infliximab, Inotuzumab, Ipilimumab, Ixekizumab, Moxetumomab, Nivolumab, Obinutuzumab,Ocrelizumab, Ofatumumab, Pembrolizumab, Polatuzumab, Rituximab, Rituximab, Sarilumab, Secukinumab, Tocilizumab, Tositumumab, Tremelimumab, Urelumab, Ustekinumab
• History of bone marrow transplantation (including chimeric antigen receptor T-cell) or solid organ transplant
• Known history of Hepatitis B or Hepatitis C (patients who have completed curative-intent anti-HCV treatments are not excluded from trial)
• Positive result on hepatitis B or C screening
• Known history of mycobacterium tuberculosis infection at risk for reactivation
• Known history of gastrointestinal perforation
• Active diverticulitis
• Multi-organ failure as determined by primary treating physicians
• Any other documented serious, active infection besides COVID-19 - including but not limited to: lobar pneumonia consistent with bacterial infection, bacteremia, culture-negative endocarditis, or current mycobacterial infection - at the discretion of primary treating physicians
• Pregnant patients or nursing mothers
• Patients who are unable to discontinue scheduled antipyretic medications, either as monotherapy (e.g., acetaminophen or ibuprofen [aspirin is acceptable]) or as part of combination therapy (e.g., hydrocodone/acetaminophen, aspirin/acetaminophen/caffeine [Excedrin®])
• CRP < 40 mg/L

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Participants in another simultaneous clinical trial
• Use of other immunomodulators
• Coinfection with the hepatitis B virus (detectable AgSup-HBV)
• Pregnancy (or planning to become pregnant during the course of the study), or lactation period
• Presence of laboratory abnormalities of grade ≥ 4.

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• mechanical ventilation for more than 24 h at randomisation
• a clinical frailty score greater than 3 before SARS-CoV-2 infection
• unlikelihood to survive beyond 48 h based on clinical assessment
• an active co-infection defined on clinical grounds (positive blood or sputum cultures)
• thrombocytopenia of less than 50 000/μL
• neutropenia of less than 1500/μL
• a history of bowel perforation or diverticulitis
• high dose systemic steroid or immunosuppressive drug use for a COVID-19-unrelated disorder.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Death deemed to be imminent and inevitable during the next 24 hours
• one or more of the participant, substitute decision maker or attending physician are not committed to full active treatment
• more than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection or more than 24 hours elapsed since ICU admission
• previous participation in this REMAP within the last 90 days
• patient has already received any dose of one or more of any form of interferon, anakinra, tocilizumab, or sarilumab during this hospitalization
• long-term therapy with any of these agents prior to this hospital admission
• patient has been randomized in a trial evaluating an immune modulation agent for proven or suspected COVID-19 infection where the protocol of that trial requires ongoing administration of study drug
• known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization
• intention to prescribe systemic corticosteroids for any reason, other than participation in the Corticosteroid domain of this platform, is an exclusion criterion to receive IFN-β1a
• known hypersensitivity to proteins produced by E. coli will result in exclusion criterion to receive anakinra
• known or suspected pregnancy is an exclusion criterion to receive the anakinra, IFN-β1a, tocilizumab, and sarilumab interventions
• a baseline alanine aminotransferase or an aspartate aminotransferase that is more than five times the upper limit of normal is an exclusion criterion to receive tocilizumab or sarilumab
• a baseline platelet count < 50 x 109 / L is an exclusion criterion to receive tocilizumab or sarilumab.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
• Patient is expected to be discharged from hospital today or tomorrow
• More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection
• Previous participation in this REMAP within the last 90 days
• More than 24 hours has elapsed since ICU admission
• Patient has already received any dose of one or more of any form of interferon, anakinra, tocilizumab, or sarilumab during this hospitalization or is on long-term therapy with any of these agents prior to this hospital admission
• Known condition or treatment resulting in ongoing immune suppression including neutropenia prior to this hospitalization
• Patient has been randomized in a trial evaluating an immune modulation agent for proven or suspected Covid-19 infection, where the protocol of that trial requires ongoing administration of study drug
• The treating clinician believes that participation in the domain would not be in the best interests of the patient
• Known hypersensitivity to an agent specified as an intervention in this domain will exclude a patient from receiving that agent
• Known or suspected pregnancy will result in exclusion from the anakinra, IFN-β1a, tocilizumab, and sarilumab interventions. It is normal clinical practice that women admitted who are in an age group in which pregnancy is possible will have a pregnancy test conducted. The results of such tests will be used to determine interpretation of this exclusion criteria
• A baseline alanine aminotransferase or an aspartate aminotransferase that is more than five times the upper limit of normal will result in exclusion from receiving tocilizumab or sarilumab
• A baseline platelet count < 50 x 10^9 / L will result in exclusion from receiving tocilizumab or sarilumab

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Known hypersensitivity to Tocilizumab or to any of their excipients, Pregnancy
• Current documented bacterial infection, Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication, Absolute neutrophil count (ANC) ≤ 1.0 x 109/L,Haemoglobin level: no limitation, Platelets (PLT) < 50 G /L
• SGOT or SGPT > 5N

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Patients with exclusion criteria to the CORIMUNO-19 cohort
• Known hypersensitivity to Tocilizumab or to any of their excipients
• Pregnancy
• Current documented bacterial infection
• Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication: Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
• Haemoglobin level: no limitation
• Platelets (PLT) < 50 G /L
• SGOT or SGPT > 5N

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Known hypersensitivity to tocilizumab or its excipients
• Patient with a life expectancy of less than 6 months
• Known active infections or other clinical condition that contra-indicate tocilizumab and cannot be treated or solved according to the judgement of the clinician
• Neutrophils <500 / mmc
• Platelets <40.000 / mmc

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• - A specific contra-indication to one of the active drug treatment arms or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient
• 
  - Patients with known hypersensitivity to tocilizumab, evidence of active tuberculosis infection or clear evidence of active bacterial, fungal, viral, or other infection (besides COVID-19) were not eligible for randomisation to tocilizumab

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

• Pregnancy or breast feeding
• Ongoing or completed mechanical ventilation
• In the opinion of the investigator, unlikely to survive for >48 hours from screening
• In the opinion of the investigator, expected overall survival due to other comorbidities less than 3 months
• Severe renal dysfunction eGFR < 30 ml/min
• Medical history including chronic liver disease with inflammation, fibrosis or cirrhosis including underlying diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis, alcoholic liver disease, autoimmune liver disease, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis, or carcinoma
• Uncontrolled hypertension Systolic BP >180 mm Hg, Diastolic BP > 110 mm Hg
• History of hypersensitivity to the study drugs
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 2 x 109/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN), platelets <100 x 109/L
• Treatment with anakinra, anti-IL 6, anti-IL-6R antagonists, Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs)/immunosuppressive agents
• Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. Ongoing acute treatment for COVID-19 with any peroral or iv steroid is permitted for up to five days before inclusion. Chronic or acute treatment with inhaled steroids is also permitted
• History of, or current autoimmune or inflammatory systemic or localized disease(s) other than rheumatoid arthritis
• Acute systemic infection
• verified by blood cultures systemic bacterial infection, systemic fungi-infection or prosthesis-related infection
• History of stem-cell or solid organ transplantation
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections
• Diagnosis of, or suspicion of HIV infection, acute hepatitis A and/or chronic hepatitis B and/or C
• Previous history of gastrointestinal ulceration or diverticulitis.
• Patients who have received immunosuppressive antibody therapy within the past 3 months, including intravenous immunoglobulin or plans to receive during the study period
• Participation in any clinical research study evaluating an investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. The use of remdesivir is permitted.
• Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Treating physician determined that death was imminent and inevitable within 24 hours
• Had active tuberculosis or bacterial, fungal, or viral infection other than SARS-CoV-2

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Pregnancy
• Allergy to tocilizumab

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• Required continuous positive airway pressure, bilevel positive airway pressure, or mechanical ventilation
• If progression to death was imminent and inevitable within 24 hours as determined by the treating physician
• Active tuberculosis or suspected active bacterial, fungal, or viral infection (other than SARS-CoV-2 or well-controlled HIV)
• Patients with comorbidities were not excluded unless the investigator determined it would preclude safe patient participation.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Exclusion criteria included ICU admission, known hypersensitivity to tocilizumab, and any condition preventing future admission to ICU, such as advanced age with multiple comorbidities, as well as the patient’s expressed will to avoid future intubation.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

• Known severe allergic reaction to tocilizumab or other monoclonal antibodies
• active tuberculosis infection
• Suspected or active bacterial, fungal, or viral infection (except treated hepatitis C or B), or any other infection except COVID-19
• Investigator deemed that the patient death was imminent and inevitable within 24 hours or judged that the patient had any serious medical conditions or laboratory abnormalities that precluded safe participation in and completion of the study
• Patients could not have received any oral anti-rejection or immunomodulatory drugs in the previous 6 months or treatment with any investigational agent (including antivirals, cell-depleting therapies, biologics, and Janus kinase inhibitors) within five half-lives or 30 days before randomisation, whichever was longer
• Patients could not have a diagnosis of immune related rheumatic disease or be receiving corticosteroids equivalent to methylprednisolone at a dose of more than 1 mg/kg per day at screening or baseline
• Absolute neutrophil count less than 500 cells per mcL, platelet count less than 50 000 cells per mcL, and alanine aminotransferase or aspartate aminotransferase concentrations more than ten times the upper limit of normal within 24 h of screening or baseline

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

• Receiving supplemental oxygen at a rate that exceeded 10 liters per minute
• Had a recent history of treatment with biologic agents or small molecule immunosuppressive therapy
• Receiving other immunosuppressive therapy that the investigator believed placed them at
• Higher risk for an infection
• had had diverticulitis

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Allergic or intolerant to any therapeutic factors used in this study
• With positive pro-calcitonin (PCT) and had an active infection (including latent or active tuberculosis (TB) infection)
• Had a history of receiving immunosuppressive drugs and corticosteroids
• With a history of active malignancies.

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• 1. Need for mechanical ventilation for 24 hours or more before the randomization
  2. Hypersensitivity to tocilizumab
  3. Patients without therapeutic perspective or in palliative care
  4. Active non-controlled infections (other than COVID-19)
  5. Neutrophil count < 0.5 x 109/L
  6. Platelet count < 50 x 109/L
  7. Liver disease, cirrhosis or elevated AST or ALT above 5 times the upper limit of normal
  8. Renal disease with estimate glomerular filtration below 30 mL/min/1.72 m2 (MDRD or CKD-EPI scores)
  9. Breastfeeding women
  10. Pregnancy
  11. Other clinical conditions that contraindicate tocilizumab, according to the attending physician

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

• 1) woman who is pregnant or lactating
• 
  2) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal(ULN
• neutropenia < 0.5×109/L
• platelet < 50×109/L
• 
  3) people diagnosed with rheumatism- and immunity-related diseases, cancer and other related diseases
• 
  4) people who are taking antirejection or immunomodulatory drugs
• 
  5) people who are allergic to tocilizumab or any excipients
• 
  6) patients with active hepatitis and tuberculosis, associated with specific bacterial and fungal infections
• 
  7) patients who have had organ transplantation
• 
  8) people with mental disorders

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported