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
  • 19 to 85 years of age and had SARS-CoV-2 infection confirmed by either nasopharyngeal swab polymerase chain reaction or serum IgM antibody
  • Patients had to have at least two of the following signs: fever (body temperature >38°C) within 72 hours before enrollment, pulmonary infiltrates, or a need for supplemental oxygen in order to maintain an oxygen saturation higher than 92%
  • At least one of the following laboratory criteria also had to be fulfilled: a C-reactive protein level higher than 50 mg per liter, a ferritin level higher than 500 ng per milliliter, a d-dimer level higher than 1000 ng per milliliter, or a lactate dehydrogenase level higher than 250 U per liter.
Exclusion criteria
  • 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
Interventions
Treatment
Tocilizumab
8 mg/kg IV single dose, maximum 800 mg
Control
Placebo

Participants
Randomized
participants :
Tocilizumab=161
Placebo=82
Characteristics of participants
N= 243
Mean age : NR
141 males
Severity : Mild: n=38 / Moderate: n=194 / Severe: n=10 Critical: n=1
Number of vaccinated participants: 0
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 willing stated in the publication:

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. Concerning the sample size, the protocol states the following: « At the outset, the target enrollment was 278 patients 83 of 92 to achieve 85% power. However, the enrollment rate significantly slowed as the pandemic surge waned in the Boston area, and in early June the decision was made to reduce the target enrollment to 243 (80% power) and the protocol was amended to reflect this change”. 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.
This study was updated on May 11th, 2022 with data extracted from the registry.