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).
On 31st December, 2019, a novel coronavirus, later named SARS-CoV-2, and whose clinical disease was to be named COVID-19, was isolated in China. First in Italy and then all over the world, viral circulation rapidly increased to a pandemic level, as defined by WHO on March 11th, 2020. In Italy, one of the most affected countries, where over 35,000 deaths have been recorded, lockdown was the only efficacious containment measure [1]. Unfortunately, hospitals soon became reservoirs of contagion [2]. In the northern Italian district of Piacenza in Emilia-Romagna, heavily hit by the shock wave of the virus, 1894 patients were hospitalized due to COVID-19 during March-April, 2020; dialysis patients were immediately identified as particularly frail. Home dialysis is the only means to allow dialysis patients to respect the lockdown, minimizing exposure to the hospital setting. In this regard, we would like to comment on our experience, from a center with a highly developed system of home dialysis. Indeed, patients on home dialysis (peritoneal dialysis [PD] and home hemodialysis [HHD]) represent 18% of our dialysis population (36/210 patients), a high figure by European standards. Our experience with home dialysis may be of particular interest, since we recorded a very high incidence of COVID-19 in patients on in-center hemodialysis (49/210 patients, 23%) [2], much higher than the overall incidence in Italy (about 3%), as recently reported by a survey of the Italian Society of Nephrology (available at: https ://sinit aly.org/ wp-conte nt/uploa ds/2020/05/2-Surve y-Covid-19-SIN-1. pdf, accessed on July 13th, 2020) involving 30,129 hemodialysis patients: among them, 1027 patients (3.41%) resulted affected by COVID-19.
This study demonstrates that, in elderly Italian participants, progression of CKD occurs more slowly than in younger patients. This implies that we may probably face an epidemic of CKD but that most of elderly patients diagnosed with CKD may not evolve to end-stage renal disease and require renal replacement therapy.
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