COVID-19
Conditions
Keywords
COVID-19
Brief summary
At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.
Detailed description
Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an exaggerated immune response. CSS can be triggered by infections or therapeutic interventions, being more severe depending on the degree and duration of immune activation. CSS is as a significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which have been subject to assessment for the treatment of haematological malignancies. Tocilizumab (intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T cell-induced severe or life-threatening CSS. Based on the experience with tocilizumab in the CSS, and that some patients infected with SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is being investigated in China and Italy, and clinical trials are being conducted/planned in these and several other countries. Real-word experience with tocilizumab IV have shown that in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to normal and respiratory function based on oxygen intake and lung opacities improved remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased in patients infected decreased significantly with tocilizumab, and lymphocytes levels also returned to normal. All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to initiate the controlled distribution of tocilizumab IV, in light of the increased interest on the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore, tocilizumab might be among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU. This large real-world cohort provides a unique opportunity to study a potential medicine during the current emergency situation, and support the findings from the Roche-sponsored Phase III study that is planned to start in early April.
Interventions
DRUGTocilizumab
Treatment with Tocilizumab
Sponsors
Roche Pharma AG
Dynamic Science S.L.
Fundacion SEIMC-GESIDA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase II, one-arm, open label, multicentre study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide oral informed consent to participate in this study. * At least 18 years of age. * Diagnosed with COVID-19 pneumonia by RT-PCR. * Have received the first dose of tocilizumab a maximum of two days before the inclusion or is candidate for tocilizumab treatment * Hospitalized or admitted to ICU
Exclusion criteria
* The patient has any other medical condition or is receiving concomitant medication that could, in the opinion of the investigator, compromise the patient's safety or collected data * Known severe allergic reactions to tocilizumab or other monoclonal antibodies * Active acute and severe infections, including tuberculosis infection * Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To calulate the time of intubation | through study completion, and average of 1 month | Calculate the mean time of intubation |
| To calculate the time with oxygen therapy | through study completion, and average of 1 month | Calculate the mean time with oxygen therapy |
| To calculate the time with Non-invasive mechanical ventilation | through study completion, and average of 1 month | Calculate the mean time with Non-invasive mechanical ventilation |
| To evaluate mortality rate | through study completion, and average of 1 month | Number of patients deaths of the total of patients included |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the requirement of additional organ support | through study completion, and average of 1 month | Percentage of patients with extracorporeal membrane oxygenation |
| To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers | through study completion, and average of 1 month | Analyze the levels of IL-6 |
| To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab | through study completion, and average of 1 month | Incidence of adverse events |
| To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity | through study completion, and average of 1 month | To evaluate the time to RT-PCR virus negativity |
| To calculate respiratory function parameters | through study completion, and average of 1 month | To calculate the mean ofPaO2/FiO2 |
| To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab | through study completion, and average of 1 month | Indicende of serious adverse events |
| To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab | through study completion, and average of 1 month | Indicende of adverse events of special interest based on dose of Tocilizumab |
| To evaluate mortality rate | through study completion, and average of 1 month | Number of patients deaths of the total of patients included based on dose of Tocilizumab |
| To evaluate respiratory function | through study completion, and average of 1 month | Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab |
| To evaluate the effect of IV tocilizumab on the serum levels of inflammatory | through study completion, and average of 1 month | Analyze the levels of CRP |
| To evaluate radiological lung extension | through study completion, and average of 1 month | Evaluate the lung extension of pneumonia |
| To evaluate radiological evolution | through study completion, and average of 1 month | Evaluate the type of lung affection |
| To describe the duration of hospitalization and ICU use | through study completion, and average of 1 month | Days of hospitalization in survivors and/or days at ICU throughout the study |
Countries
Spain
Outcome results
None listed