Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

• Status: Terminated
• Trial end date: 2020-09-27
• Target enrollment: 0
• Participant gender: All

Summary

The mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets.

There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS.

The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Inselspital, Berne
• Collaborator: Roche Pharma AG

Criteria

Inclusion Criteria:

I (first step):

• Admission to hospital

• Male or non-pregnant female, ≥60 years of age or ≥30 years of age plus one or more known risk factors (arterial hypertension, diabetes mellitus, coronary heart disease, heart failure, pre-existing chronic pulmonary disease)

• Confirmed SARS-CoV infection

• Radiographic evidence compatible with Covid-19 pneumonia (X-ray/CT scan, etc.)

• Signed Informed Consent Form

II (second step; indication for intervention):

• CRP ≥50mg/L plus 3 out of the following 5 criteria need to be fulfilled:

• Respiration Rate ≥25

• SpO2 <93% (on ambient air)

• PaO2 <65 mmHg

• Persistent or increasing dyspnoea as defined by a one point increase on the mMRC dyspnoea scale (over 1 hour)

• Persistent or increasing oxygen demand (over 1 hour)

Exclusion Criteria:

I (first step):

• Patients >80 years of age

• Patient included in any other interventional trial

• Indication for imminent or immediate transfer to ICU

• Treatment with TCZ (or other anti-IL-6R treatment) within 4 weeks prior to baseline

• Uncontrolled bacterial superinfection according to investigator

• History of severe allergic reaction to TCZ

• History of diverticulitis requiring antibiotic treatment or history of colon perforation

• History of primary immunodeficiency (e.g. CVID) or progressing malignancy

• History of chronic liver disease (>Child-Pugh A, or according to investigator)

II (second step; contraindication for intervention):

• Alanine transaminase/aspartate transaminase (ALT/AST) >5 times of the upper limit of normal

• Hemoglobin <80 g/L

• Leukocytes <2.0 G/L

• Absolute neutrophil count <1.0 G/L

• Platelets <50 G/L