The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

Study Overview
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Brief Summary
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Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

Detailed Description
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Study design This is a multicenter, two arms, 2:1 (treatment: control) open-label randomized control study with a drug approved for another indication in Israel. All the patients enrolled will be treated with tocilizumab or not. One-month mortality rate is the primary endpoint. One arm will be the study drug anti-IL6R (Tocilizumab (Actmera)) 8 mg/kg given IV during one hour once. The placebo will be a 100 ml saline IV infusion administered along one hour.

Official Title
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The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

Conditions
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Covid19 Pneumonia

Intervention / Treatment
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* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any gender Age 18 and older Informed consent for participation in the study Virological diagnosis of Sars-CoV2 infection (PCR) Acute respiratory failure Radiographic pneumonia, defined as any/ changing new lung infiltrate Patient breathing spontaneously, required more than 50% oxygen and MEWS score > 7. If intubated, intubated less than 24 hours with PaO2/Fio2 ratio ≤ 200 and PEEP ≥ 5 cm H2O. Exclusion Criteria: Known hypersensitivity to tocilizumab or its excipients Patient with a life expectancy of less than 6 months. Known active infections or other clinical condition that contra-indicate tocilizumab and cannot be treated or solved according to the judgement of the clinician. Neutrophils <500 / mmc Platelets <40.000 / mmc

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: Tocilizumab treatment group<br>Treatment: intravenous administration of monoclonal anti body anti- IL6R. The dose is 8 mg/kg up to total dose of 800 mg. | Drug: Tocilizumab<br>* The placebo treatment arm will include 100 ml of normal saline administered along 60 min<br>* Other names: Placebo;|
| Placebo Comparator: Placebo group<br>Placebo. intravenous administration of 100 ml of normal saline. | Drug: Tocilizumab<br>* The placebo treatment arm will include 100 ml of normal saline administered along 60 min<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | One-month mortality rate . | One-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Cytokine storm, IL-6