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).

Aims:The aim of this study was to describe the epidemiology, mechanisms, management, and outcomes of coronary artery perforation during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods and results:We included 1,811 consecutive patients undergoing CTO PCI at five centres between 2011 and 2018. Coronary perforation was observed in n=99 (5.5%). Patients with perforation were older, had a higher J-CTO score, more often required antegrade dissection/re-entry and the retrograde approach, and had lower success rates. The frequency of Ellis type I, II, III and III "cavity spilling" perforations was 11%, 46%, 28%, and 14%, respectively. In 48% of cases, perforation involved the CTO vessel, while the retrograde approach was responsible for 46% of cases. In 53% of cases perforations required intervention. The most frequently applied management strategies included clinical observation (47%), covered stent implantation (25%), balloon occlusion (9%), and coil/fat embolisation (9%). Tamponade was observed in 20/99 (20%) perforation cases. Ellis type III perforations were most frequently observed at the CTO site. These were accountable for 16/20 tamponades and 3/5 deaths. In-hospital mortality was 5.1% vs 0.3% in patients with versus those without perforation (p<0.001). Older age, occlusion length >20 mm, rotational atherectomy, antegrade dissection/re-entry, and the retrograde approach were independently associated with coronary perforation. Patients with perforation suffered an increased incidence of target vessel failure on short-term follow-up.Conclusions: Coronary perforation is observed in a non-negligible proportion of CTO PCIs, often requires intervention, and is associated with tamponade and mortality in a minority of patients. CTO vessel-related perforations are associated with the highest burden of morbidity and mortality.

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