COVID-19 Pneumonia
Conditions
Keywords
COVID-19, pneumonia, tocilizumab, Interleukin-6
Brief summary
This study project includes a single-arm phase 2 study and a parallel cohort study, enrolling patients with COVID-19 pneumonia.
Detailed description
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: 1. emergency conditions or infrastructural or operational limits prevented registration before the administration of the experimental drug or 2. they had been intubated more than 24 hours before registration or 3. 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.
Interventions
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.
Sponsors
National Cancer Institute, Naples
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a multicenter, single-arm, open-label, phase 2 study. All the patients enrolled are treated with tocilizumab
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Any gender 2. No age limit 3. 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) 4. Virological diagnosis of SARS-CoV-2 infection (real-time PCR) 5. Hospitalized due to clinical/instrumental diagnosis of pneumonia 6. Oxygen saturation at rest in ambient air ≤93% or requiring oxygen therapy or mechanical ventilation either non invasive or invasive (intubated) 7. Patients with criteria #4 and #5 who have been already treated with tocilizumab before registration are eligible for the observational retrospective cohort
Exclusion criteria
1. Known hypersensitivity to tocilizumab or its excipients 2. Known active infections or other clinical condition that contraindicate tocilizumab and cannot be treated or solved according to the judgement of the clinician 3. ALT / AST\> 5 times the upper limit of the normality 4. Neutrophils \<500 / mmc 5. Platelets \<50.000 / mmc 6. Bowel diverticulitis or perforation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lethality rate two weeks after registration | up to 15 days | 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. |
| Lethality rate one month after registration | up to 1 month | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRP (C-reactive protein) level | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | CRP is assessed by routinely used determination of CRP |
| PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | calculated from arterial blood gas analyses (values from 300 to 100) |
| Change of the SOFA (Sequential Organ Failure Assessment) | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | 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. |
| Interleukin-6 level | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | IL-6 levels will be assessed using commercial ELISA method. |
| Radiological response | at baseline (optional), after seven days and if clinically indicated (up to 1 month) | Thoracic CT scan or Chest XR |
| Duration of hospitalization | from baseline up to patient's discharge (up to 1 month) | Days of hospitalization |
| Remission of respiratory symptoms | up to 1 month | time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation |
| Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 | during treatment and up to 30 days after the last treatment dose | graded according to CTCAE citeria (v5.0) |
| Lymphocyte count | baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month | Lymphocyte count assessed by routinely used determination of blood count |
Countries
Italy
Outcome results
None listed