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

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

Набор данных


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); (NCT04317092).
Данные стали доступны1 янв 2020
ИздательFigshare - Springer