Publication Rosas I, medRxiv, 2020 (preprint)
Dates: 2020-04-03 to 2020-07-28
Funding: Mixed (F. Hoffmann-La Roche Ltd; Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority)
Conflict of interest: Yes
Blinding: double blinding
Multicenter / Canada, Denmark, France, Germany, Italy, Netherlands, Spain, UK, USA |
Follow-up duration (days): 60
|Inclusion criteria||Patients 18 years or older with severe COVID-19 pneumonia confirmed by positive polymerase chain reaction test in any body fluid and evidenced by bilateral chest infiltrates on chest x-ray or computed tomography were enrolled. Eligible patients had blood oxygen saturation ≤93% or partial pressure of oxygen/fraction of inspired oxygen <300 mm/Hg. Informed consent was obtained for all enrolled patients.|
Patients were excluded if the treating physician determined that death was imminent and inevitable within 24 hours or if they had active tuberculosis or bacterial, fungal, or viral infection other than SARS-CoV-2.
Known severe allergic reactions to TCZ or other monoclonal antibodies Active tuberculosis (TB) infection 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 TCZ) with the past 3 months Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor) Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination Treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization (investigational COVID-19 antivirals may be permitted if approved by Medial Monitor) 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 screening (per local lab) Absolute neutrophil count (ANC) < 1000/mL at screening (per local lab) Platelet count < 50,000/mL at screening (per local lab)
Co-Intervention: Standard care
Duration : 1 day
Duration : 1 day
452 participants (n1=301 / n2= 151)
|Characteristics of participants|
Mean age : 60.8
Severity : Mild: n=15 / Moderate: n=122/ Severe: n=133 Critical: n=168
|In the register|
|In the report|
Clinical status assessed on a 7-category ordinal scale at day 28
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
In addition to all available versions of the pre-print article, the study registry and supplementary appendix were used in data extraction and risk of bias assessment. |
Patients in the Tocilizumab group received a second dose only if their condition did not improve or worsened.
The study achieved the target sample size prespecified in the registry. There is no change from the trial registration in the intervention and control treatments as well as primary outcome. Some secondary outcomes in the registry were not reported in the pre-print article, particularly regarding the 60-day timepoint as well.
The sponsor (Hoffman-La Roche Ltd.) played a prominent role, with writing support for the authors provided by Sara Duggan, Ph.D., of ApotheCom, funded by F. Hoffmann-La Roche Ltd. Three authors were employees of Roche Products Ltd.