• Critical COVID-19, defined by mechanical ventilation and/or expected death within 24 hours
• pregnancy
• enrollment in another interventional clinical trial
• chronic administration of certain immunosuppressive drugs (e.g., chronic prednisone > 10 mg/day, JAK inhibitors, or immunosuppressive biologics)

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported

• 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

• Patients who require mechanical ventilation at the time of inclusion
• AST / ALT values > 5 folds the ULN.
• Absolute neutrophil count below 500 cells/mm3
• Absolute platelet count below 50,000 cells/mm3
• Superimposed infection by pathogens other than COVID-19
• Complicated diverticulitis or intestinal perforation
• Immunosuppressive antirejection therapy
• Pregnancy or lactation
• Previous treatment with TCZ or SAR
• Contraindication to SAR or excipients
• Comorbidities that can likely lead to an unfavorable result.

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 Sarilumab 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 at least one of the following: in the investigator’s opinion, a low probability of surviving 48 hours or remaining at the investigational site beyond 48 hours
• 
  - Dysfunction of >=2 organ systems or need for extracorporeal life support or renal replacement therapy at screening
• 
  - Absolute neutrophil count <2000/mm3
• aspartate aminotransferase or alanine aminotransferase (ALT) exceeding 5-fold upper limit of normal (ULN) at screening
• 
  - Platelets <50,000/mm3 at screening
• 
  - Known active, incompletely treated, suspected or known extrapulmonary tuberculosis
• 
  - Prior or concurrent use of immunosuppressants at screening, including, but not limited to, IL-6 inhibitors or Janus kinase inhibitors within 30 days of baseline
• 
  - Anti-CD20 agents without evidence of B-cell recovery to baseline levels or IL-1 receptor antagonist (anakinra) within 1 week of baseline
• 
  - Abatacept within 8 weeks of baseline
• tumor necrosis factor a inhibitors within 2–8 weeks of baseline
• 
  - Alkylating agents, including cyclophosphamide, within 6 months of baseline
• 
  - Cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or methotrexate within 4 weeks of baseline
• 
  - Intravenous (IV) immunoglobulin within 5 months of baseline
• 
  - Use of systemic chronic (eg, oral) corticosteroids for a condition not related to COVID-19 at doses higher than prednisone 10 mg/day or equivalent at screening
• 
  - Suspected or known active systemic bacterial or fungal infections within 4 weeks of screening

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

• ICU at admission
• Pregnant women

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Presence of ARDS requiring HFNO or mechanical ventilation at randomization (or expected to be started in the first 24 hours after randomization as deemed by decision of the investigator)
• Patients in which the decision was made to not progress to mechanical ventilation in the event of clinical deterioration

Protocol

Yes. In English

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• Patients with high oxygen requirements (including face mask with reservoir bag, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation)
• Had been on treatment with CS for more than 1 day
• Were admitted to the intensive care unit (ICU)
• Pregnant or lactating
• Had allergy or hypersensitivity to sarilumab or CS
• Had received immunosuppressive monoclonal antibody therapy within the past 5 months
• AST/ALT values more than 10 x ULN
• Neutropenia (less than 0.5 x 109/L)
• Severe thrombocytopenia (less than 50 x 109/L)
• Sepsis caused by an alternative pathogen
• Diverticulitis with risk of perforation
• Ongoing infectious dermatitis.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• In the opinion of the investigator, not expected to survive for more than 48 hoursfrom screening
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count <2000 mm3, aspartate aminotransferase or alanine aminotransferase >5x upper limit of normal, platelets <50,000 per mm3
• Treatment with anti IL-6, anti IL-6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with the simultaneous combination of leflunomide and methotrexate
• Exclusion criteria related to tuberculosis (TB)a. Known active TB or a history of incompletely treated TB b. Suspected or known extrapulmonary TB
• Patients with suspected or known active systemic bacterial or fungal infections Note: Patients with a history of positive bacterial or fungal cultures but on enrollment do not have suspected or known active systemic bacterial or fungal infections may be enrolled
• Participation in a double-blind clinical research study evaluating an investigational product or therapy within 3 months and less than 5 half-lives of investigational product prior to the screening visit Exception: The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, emergency use authorization, compassionate use protocol, or open-label use is permitted
• Any physical examination findings, and/or history of any illness, concomitant medications, or recent live vaccines 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
• Known systemic hypersensitivity to sarilumab or the excipients of the drug product

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• In the opinion of the investigator, not expected to survive for more than 48 hoursfrom screening
• Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count <2000 mm3, aspartate aminotransferase or alanine aminotransferase >5x upper limit of normal, platelets <50,000 per mm3
• Treatment with anti IL 6, anti IL 6R antagonists, or with Janus kinase inhibitors (JAKi) in the past 30 days or plans to receive during the study period
• Current treatment with the simultaneous combination of leflunomide and methotrexate
• Exclusion criteria related to tuberculosis (TB)a. Known active TB or a history of incompletely treated TB b. Suspected or known extrapulmonary TB
• Patients with suspected or known active systemic bacterial or fungal infections Note: Patients with a history of positive bacterial or fungal cultures but on enrollment do not have suspected or known active systemic bacterial or fungal infections may be enrolled
• Participation in a double-blind clinical research study evaluating an investigational product or therapy within 3 months and less than 5 half-lives of investigational product prior to the screening visit Exception: The use of remdesivir, hydroxychloroquine, or other treatments being used for COVID-19 treatments in the context of an open-label study, emergency use authorization, compassionate use protocol, or open-label use is permitted
• Any physical examination findings, and/or history of any illness, concomitant medications, or recent live vaccines 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
• Known systemic hypersensitivity to sarilumab or the excipients of the drug product

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes