Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

Study Overview
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Brief Summary
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The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.

Official Title
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An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years Informed consent for participation in the study Real time polymerase chain reaction (PCR) diagnosis of Sars-CoV2 infection Hospitalization due to clinical / instrumental diagnosis (high resolution chest CT scan or chest x-ray or pulmonary ultrasound) Presence of acute respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) between 200 and 300 mm/Hg Presence of exaggerated inflammatory response defined by the presence of at least 1 of the following criteria: At least one body temperature measurement >38° C in the past two days; Serum CRP greater than or equal to 10 mg/dl; CRP increase of at least twice the basal value Exclusion Criteria: Patients with respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) <200 mm/Hg or Patients in non-invasive ventilation or Patients in invasive ventilation or presence of shock or presence of concomitant organ failure that requires admission to the Intensive Care Unit Severe heart and kidney failure Pregnant or breastfeeding patient Patient who, in the opinion of the clinician or by the patient's express will, will not go to intensive care regardless of the evolution of the lung picture. Known hypersensitivity to TCZ or its excipients Patient being treated with immuno-depressors or anti-rejection drugs Known active infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment glutamate-pyruvate transaminase (GPT) or glutamine oxaloacetic transaminase (GOT) > 5 times the upper limit of the norm Neutrophils <500 /mmc Platelets <50.000 /mmc Diverticulitis or intestinal perforation Suspicion of latent tuberculosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Tocilizumab within 8 hours from entering the study + standard of care; 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours | Drug: Tocilizumab<br>* In case of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours<br>* Other names: Standard of care;|
| Other: Control Arm<br>Standard of care; In the event of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours | Drug: Tocilizumab<br>* In case of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours<br>* Other names: Standard of care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation | Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours | two weeks from participants' allocation to study arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death from any cause | Death | Two weeks from participants' allocation to study arm | 
| Tocilizumab toxicity | Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale | Two weeks from participants' allocation to study arm | 
| Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment | Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment | Two weeks from participants' allocation to study arm | 
| Evaluate the progress of the PaO2 / FiO2 ratio | Changes from baseline of the PaO2 / FiO2 ratio | Two weeks from participants' allocation to study arm | 
| Evaluate the trend over time of the lymphocyte count | Changes from baseline of the lymphocyte count | Two weeks from participants' allocation to study arm |