Tocilizumab in COVID-19 Pneumonia (TOCIVID-19)

Study Overview
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Brief Summary
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This study project includes a single-arm phase 2 study and a parallel cohort study, enrolling patients with COVID-19 pneumonia.

Detailed Description
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Phase 2 study: this is a multicenter, single-arm, open-label, phase 2 study. All the patients enrolled are treated with tocilizumab. Two-week (14 days) and one-month (30 days) lethality rates are the co-primary endpoints. The parallel cohort includes patients who are treated with tocilizumab and cannot enter the phase 2 study because: emergency conditions or infrastructural or operational limits prevented registration before the administration of the experimental drug or they had been intubated more than 24 hours before registration or the phase 2 study has been closed due to reached sample size. This means that, after closure of the phase 2 enrolment, patients who might be eligible for the phase 2 study will be included in the observational cohort study. The same information planned for the phase 2 cohort is required also for the parallel cohort study whose sample size is not defined a priori, and that will close at the end of the overall project. All the patients enrolled are treated with tocilizumab. In both study groups (phase 2 and parallel cohort), participants receive one dose of Tocilizumab 8 mg/kg (up to a maximum of 800mg per dose). A second administration (same dose) can be given after 12 hours if respiratory function has not recovered, at discretion of the Investigator.

Official Title
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Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Tocilizumab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any gender No age limit Informed consent for participation in the study (consent can be oral if a written consent cannot be expressed. If the subject is incapable of giving an informed consent and an authorized representative is not available without a delay that would, in the opinion of the Investigator, compromise the potential life-saving effect of the treatment this can be administered without consent. Consent to remain in the research should be sought as soon the conditions of the patient will allow it) Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Hospitalized due to clinical/instrumental diagnosis of pneumonia Oxygen saturation at rest in ambient air ≤93% or requiring oxygen therapy or mechanical ventilation either non invasive or invasive (intubated) Patients with criteria #4 and #5 who have been already treated with tocilizumab before registration are eligible for the observational retrospective cohort Exclusion Criteria: Known hypersensitivity to tocilizumab or its excipients Known active infections or other clinical condition that contraindicate tocilizumab and cannot be treated or solved according to the judgement of the clinician ALT / AST> 5 times the upper limit of the normality Neutrophils <500 / mmc Platelets <50.000 / mmc Bowel diverticulitis or perforation
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
Intervention Model: Single Group Assignment
Interventional Model Description: This is a multicenter, single-arm, open-label, phase 2 study. All the patients enrolled are treated with tocilizumab
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tocilizumab treatment<br>All the patients enrolled are treated with tocilizumab. | Drug: Tocilizumab Injection<br>* Tocilizumab 8 mg/kg (up to a maximum of 800mg per dose). A second administration (same dose) can be given after 12 hours if respiratory function has not recovered, at discretion of the Investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lethality rate two weeks after registration | 2-week lethality is defined as the ratio of the number of subjects dead within 14 days from study start out of phase 2 patients with baseline information. | up to 15 days | 
| Lethality rate one month after registration | 1-month lethality is defined as the ratio of the number of subjects dead within 30 days from study start out of phase 2 patients with baseline information. | up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 level | IL-6 levels will be assessed using commercial ELISA method. | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 
| Lymphocyte count | Lymphocyte count assessed by routinely used determination of blood count | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 
| CRP (C-reactive protein) level | CRP is assessed by routinely used determination of CRP | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 
| PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) | calculated from arterial blood gas analyses (values from 300 to 100) | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 
| Change of the SOFA (Sequential Organ Failure Assessment) | It evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24. | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 
| Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 | graded according to CTCAE citeria (v5.0) | during treatment and up to 30 days after the last treatment dose | 
| Radiological response | Thoracic CT scan or Chest XR | at baseline (optional), after seven days and if clinically indicated (up to 1 month) | 
| Duration of hospitalization | Days of hospitalization | from baseline up to patient's discharge (up to 1 month) | 
| Remission of respiratory symptoms | time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation | up to 1 month | 
| Remission of respiratory symptoms | time to definitive extubation calculated from intubation (any time occurred) to extubation in days | up to 1 month | 
| Remission of respiratory symptoms | time to independence from non-invasive mechanical ventilation calculated in days | up to 1 month | 
| Remission of respiratory symptoms | time to independence from oxygen therapy in days | up to 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, pneumonia, tocilizumab, Interleukin-6