Treatment with tocilizumab did not lead to improvement in clinical status and did not lower mortality at 28 days compared with placebo in hospitalized patients with severe pneumonia related to COVID-19, according to study results in the New England Journal of Medicine.
Investigators of this phase 3 trial (COVACTA; ClinicalTrials.gov Identifier: NCT04320615) randomly assigned hospitalized patients with severe COVID-19 pneumonia to either a single intravenous tocilizumab infusion at 8 mg per kg of body weight (n=294) or placebo (n=144). A second dose of the assigned therapies was administered to approximately 25% of patients 8 to 24 hours following the first treatment dose.
The investigators assessed clinical status at 28 days using an ordinal scale ranging from 1, defined as discharged or ready for discharge, to 7, defined as death. A number 2 on the scale represented hospitalization in a non-intensive care unit (ICU) without supplemental oxygen, 3 represented non-ICU hospitalization with supplemental oxygen, 4 was ICU or non-ICU hospitalization with noninvasive ventilation or high-flow oxygen, 5 represented ICU hospitalization with intubation and mechanical ventilation, and 6 was ICU hospitalization with extracorporeal membrane oxygenation or mechanical ventilation and additional organ support
Median ages in the tocilizumab and placebo groups were 60.9 and 60.6 years, respectively. At day 28, the median value for clinical status according to the ordinal scale was 1.0 (95% CI, 1.0-1.0) in the tocilizumab group vs 2.0 (95% CI, 1.0-4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P =.31). Serious adverse events were reported in 34.9% of patients in the tocilizumab group vs 38.5% of patients in in the placebo group. There was no difference between the 2 groups in terms of the 28-day mortality rate 19.7% for tocilizumab vs 19.4% for placebo; weighted difference, 0.3 percentage points; 95% CI, -7.6 to 8.2; P =.94).
Some limitations of the ordinal scale used in this study was its sensitivity to local clinical practice differences, insensitivity to events prior to the assessment time point, as well as lack of an established minimum clinically important difference for treatment effect.
Overall, the findings from this study, in addition to other clinical trials, emphasize “the need for effective treatments for patients with severe COVID-19 pneumonia” as this “continues to be a major challenge at this point in the pandemic.”
Disclosure: This clinical trial was supported by F. Hoffmann–La Roche. Please see the original reference for a full list of authors’ disclosures.
Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N Engl J Med. Published online February 25, 2021. doi:10.1056/NEJMoa2028700