Publication Soin AS, Lancet Respir Med, 2021 (published paper)
Dates: 2020-05-30 to 2020-08-31
Funding: Mixed (Medanta Institute of Education and Research; Roche India; Cipla India; Action COVID-19 India)
Conflict of interest: Yes
Multicenter / India |
Follow-up duration (days): 30
1. Patients aged 18 years or older; a
2. Admitted to hospital with SARS-CoV-2 infection confirmed by WHO criteria (positive PCR test on any specimen);
3. Moderate to severe disease defined according to the Indian MoHFW clinical management protocol for COVID-19.
Moderate defined as respiratory rate 15–30 per min [revised to 24 per min on June 13, 2020] and blood oxygen saturation [SpO2] 90–94%
Severe defined as respiratory rate >/=30 per min or SpO2 <90% in ambient air, or ARDS or septic shock
1. Known severe allergic reaction to tocilizumab or other monoclonal antibodies; active tuberculosis infection;
2. Suspected or active bacterial, fungal, or viral infection (except treated hepatitis C or B), or any other infection except COVID-19;
3. 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;
4. 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;
5. 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;
6. 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.
6 mg/kg IV infusion, maximun 480 mg/day, a second infusion could be administered within 12 hours to 7 days after the first dose.
Standard care ( / )
Definition of Standard care: Standard care was provided according to the protocols at the individual study sites. Corticosteroids equivalent to methylprednisolone at a dose of 1 mg/kg or less were permitted if deemed necessary by the treating physician. Supplemental oxygen was recommended to treat hypoxia, and high-flow nasal cannula, non-invasive ventilation, and mechanical ventilation could be considered if hypoxia and respiratory distress progressed. Treatments for shock or hypovolaemia, symptoms such as fever and myalgia, and comorbid conditions could be administered if deemed necessary by the treating physician.
180 participants (n1=90 / n2= 90)
|Characteristics of participants|
Mean age : NR
Severity : Mild: n=0 / Moderate: n=161/ Severe: n=48 Critical: n=9
|In the register|
Proportion of subjects showing progressive COVID 19 disease from moderate to severe, or from severe disease to death (up to day 14)
|In the report|
Proportion of patients with progression of COVID-19 from moderate to severe or from severe to death up to day 14
Yes. In English
|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
|General comment||In addition to all available version of the published article, the study registry and protocol were used in data extraction and risk of bias assessment. This is an unmasked study with no placebo. There is no change from the trial registration in the intervention and control treatments. Primary and secondary efficacy analyses were done in the modified intention-to-treat population (i.e. 179 patients), which included all randomly assigned patients who had at least one post-baseline assessment for the primary endpoint. Overall safety (mortality, adverse and serious adverse events) was assessed in all randomly assigned patients (i.e. 180 patients). Conversion to negative RT-PCR, stated as an outcome in the protocol and article, was not reported.|