Pre-emptive tocilizumab in hypoxic COVID-19 patients, a prospective randomized trial

This trial aims to develop an effective treatment strategy for COVID-19 patients with hypoxia OR other signs of hyperinflammation (ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours). The rationale for tocilizumab is: 1) Patients with respiratory failure caused by COVID-19 have a dismal prognosis; 2) The hyper inflammatory state in COVID-19 patients is a main reason for respiratory insufficiency and dead; 3) Tocilizumab is an effective drug to control cytokine storms without hampering the functional immune response; 4) Extensive experience is present with tocilizumab in the clinical setting with cytokine release syndromes (e.g. after CAR-T cell therapy).
The rationale to apply tocilizumab in the pre-emptive phase i.e. at the moment of hypoxia (defined according to cytokine release syndrome (CRS) grade II), or other signs of hyperinflammation (ferritin >2000 μg/L or doubling of serum ferritin in 20-48 hours), is to modulate the cytokine storm at an early phase before the phase of respiratory failure is reached. This is in line with the early application of tocilizumab in the clinical setting to modulate cytokine storms after CAR-T cell therapy.

Based on literature we assume a 20% day 30 mortality of patients admitted to the hospital ward with COVID-19. We aim to lower this day 30 mortality to 10%.

at entry, prior to first infusion, and 24h, 72h, 1 week, 2 weeks, 3 months after first infusion

Patients in this study are treated with intravenous tociluzumab: 8 mg/kg (maximum dose 800 mg), which can be repeated at the same dose after 8 hours if the hypoxia has not improved. This is the approved dose for cytokine release syndrome.