Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

  • Francesco Perrone (投稿者)
  • Maria Carmela Piccirillo (投稿者)
  • Paolo Antonio Ascierto (投稿者)
  • Carlo Salvarani (投稿者)
  • Roberto Parrella (投稿者)
  • Anna Maria Marata (投稿者)
  • Patrizia Popoli (投稿者)
  • Laurenzia Ferraris (投稿者)
  • Massimiliano M. Marrocco-Trischitta (投稿者)
  • Diego Ripamonti (投稿者)
  • Francesca Binda (投稿者)
  • Paolo Bonfanti (投稿者)
  • Nicola Squillace (投稿者)
  • Francesco Castelli (投稿者)
  • Maria Lorenza Muiesan (投稿者)
  • Miriam Lichtner (投稿者)
  • Carlo Calzetti (投稿者)
  • Nicola Duccio Salerno (投稿者)
  • Luigi Atripaldi (投稿者)
  • Marco Cascella (投稿者)
  • Massimo Costantini (投稿者)
  • Giovanni Dolci (投稿者)
  • Nicola Facciolongo (投稿者)
  • Fiorentino Fraganza (投稿者)
  • Marco Massari (投稿者)
  • Vincenzo Montesarchio (投稿者)
  • Cristina Mussini (投稿者)
  • Emanuele Alberto Negri (投稿者)
  • Gerardo Botti (投稿者)
  • Claudia Cardone (投稿者)
  • Piera Gargiulo (投稿者)
  • Adriano Gravina (投稿者)
  • Clorinda Schettino (投稿者)
  • Laura Arenare (投稿者)
  • Paolo Chiodini (投稿者)
  • Ciro Gallo (投稿者)

数据集

描述

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).
可用的日期1 一月 2020
出版商Figshare - Springer

引用此