Trial NCT04356937
Publication Stone JH, N Engl J Med, 2020 (published paper)
Dates: 2020-04-20 to 2020-06-15
Funding: Private (Genentech)
Conflict of interest: Yes
Methods | |
RCT Blinding: double blinding | |
Location :
Multicenter / USA Follow-up duration (days): 28 | |
Inclusion criteria | 1. Age > 18 and < 86 years old
2. Male or female gender 3. Confirmed SARS-CoV-2 infection by nasopharyngeal swab PCR or serum assay for IgM antibody 4. Requiring hospital but not mechanical ventilation Oxygen supplementation not greater than 10L delivered by any device 5. WITH evidence of severe COVID- 19 (at least 2 of the following): • Fever > 38C within 72 hours • Unable to provide verbal informed consent or have verbal agreement to participate through attestation and signature of a Witness required, as outlined in the Partners IRB’s Table for Consenting in COVID Research that is More than Minimal Risk. • Patients between the ages of 79 and 86 will be excluded if they have NYHA Class III/IV heart 32 of 92 • Pulmonary infiltrate on chest X ray • Need for supplemental O2 to maintain saturation > 92% AND at least 1 of the following: • Ferritin > 500 ng/ml • CRP > 50 mg/L • LDH >250 U/L • D-dimer > 1000 ng/mL |
Exclusion criteria | Unable to provide verbal informed consent or have verbal agreement to participate through attestation and signature of a Witness required, as outlined in the Partners IRB’s Table for Consenting in COVID Research that is More than Minimal Risk.
• Patients between the ages of 79 and 86 will be excluded if they have NYHA Class III/IV heart 32 of 92 • Pulmonary infiltrate on chest X ray • Need for supplemental O2 to maintain saturation > 92% AND at least 1 of the following: • Ferritin > 500 ng/ml • CRP > 50 mg/L • LDH >250 U/L • D-dimer > 1000 ng/mL failure, insulin-dependent diabetes mellitus, angina, or treatment of a malignancy (excluding nonmelanoma skin cancer) within six months • Uncontrolled bacterial, fungal, or non-COVID viral infection • Active tuberculosis (see appendix B) • Any prior investigational immunosuppressive therapy within 28-days or 3 half-lives of the agent (for instance with biologic or JAK inhibitor) • Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk • Receipt of intravenous tocilizumab for the treatment of a non-COVID condition within three weeks of the first COVID symptom • History of hypersensitivity to tocilizumab • Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk • Treatment with other biologic or small-molecule immunosuppressive therapy such as IL1R-antagonism, JAK inhibition, or other agents. • Treatment with convalescent plasma** • History of diverticulitis or bowel perforation • ANC <500, Platelets <50,000* • AST/ALT > 5X ULN |
Interventions | |
Treatment
Tocilizumab 8 mg/kg IV once off, maximum 800 mg |
|
Control
Placebo Duration : 1 day | |
Participants | |
Randomized 243 participants (n1=161 / n2= 82) | |
Characteristics of participants N=243 Mean age : NR 141 males Severity : Mild: n=38 / Moderate: n=194/ Severe: n=10 Critical: n=1 | |
Primary outcome | |
In the register Time from administration of the investigational agent (or placebo) to requiring mechanical ventilation and intubation, or death for subjects who die prior to intubation [ Time Frame: 28 days ] | |
In the report Intubation (or death, for patients who died before intubation) after administration of tocilizumab or placebo, assessed in a time-to-event analysis | |
Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Low |
General comment | In addition to the published article, the trial registry, study protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. The study did not achieve the sample size recorded in the trial registry. There were no other notable differences in study population, procedures, treatments or outcomes between the published article and the trial registry, study protocol and statistical analysis plan. |