Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
Posted on 2020-10-22 - 03:28
Abstract Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
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Perrone, Francesco; Piccirillo, Maria Carmela; Ascierto, Paolo Antonio; Salvarani, Carlo; Parrella, Roberto; Marata, Anna Maria; et al. (2020). Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5182700.v1
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AUTHORS (36)
FP
Francesco Perrone
MP
Maria Carmela Piccirillo
PA
Paolo Antonio Ascierto
CS
Carlo Salvarani
RP
Roberto Parrella
AM
Anna Maria Marata
PP
Patrizia Popoli
LF
Laurenzia Ferraris
MM
Massimiliano M. Marrocco-Trischitta
DR
Diego Ripamonti
FB
Francesca Binda
PB
Paolo Bonfanti
NS
Nicola Squillace
FC
Francesco Castelli
MM
Maria Lorenza Muiesan
ML
Miriam Lichtner
CC
Carlo Calzetti
NS
Nicola Duccio Salerno
LA
Luigi Atripaldi
MC
Marco Cascella