Clinical Trial to Evaluate the Effectiveness and Safety of Tocilizumab for Treating Patients With COVID-19 Pneumonia
- Registration Number
- NCT04445272
- Lead Sponsor
- Fundacion SEIMC-GESIDA
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 495
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tocilizumab Tocilizumab Patients will receive IV tocilizumab as per clinical practice and at the discretion of treating investigator, following the posology indicated in the SmPC, or the recommendations proposed by the Spanish Ministry of Health: The recommended posology by the SmPC is 8 mg per kg in patients weighing greater than or equal to 30 kg or 12 mg per kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. The recommendations of the Spanish Ministry of Health: Patients more than 80 kg: first dose 600 mg; second dose 600 mg. Patients less than 80 kg: first dose 600 mg; second dose 400 mg. A third dose might be considered 16 to 24 hours after if: fever persists or a worsening of the laboratory parameters Given the exceptionality of the situation modification of doses according to the physician experience will be allowed.
- Primary Outcome Measures
Name Time Method 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 calulate the time of intubation through study completion, and average of 1 month Calculate the mean time of intubation
To evaluate mortality rate through study completion, and average of 1 month Number of patients deaths of the total of patients included
To calculate the time with oxygen therapy through study completion, and average of 1 month Calculate the mean time with oxygen therapy
- Secondary Outcome Measures
Name Time Method 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 calculate respiratory function parameters through study completion, and average of 1 month To calculate the mean of SaO2/FiO2
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
To evaluate the requirement of additional organ support through study completion, and average of 1 month Percentage of patients with other support therapy
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 by dose of Tocilizumab
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 evaluate the effect of IV tocilizumab on the serum levels of inflammatory through study completion, and average of 1 month Analyze the levels of ferritin
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 based on dose of Tocilizumab
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 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 evaluate respiratory function through study completion, and average of 1 month Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment
To evaluate mortality rate through study completion, and average of 1 month Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment
Trial Locations
- Locations (42)
Hospital Universitario Rey Juan Carlos
🇪🇸Móstoles, Madrid, Spain
Hospital Universitario Marqués Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Clínic i Provincial Barcelona
🇪🇸Barcelona, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Hospital Rey Juan Carlos
🇪🇸Móstoles, Madrid, Spain
Hospital Universitario de Getafe
🇪🇸Getafe, Madrid, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Infanta Sofía
🇪🇸San Sebastián De Los Reyes, Madrid, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Infanta Cristina
🇪🇸Badajoz, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Hospital Universitario Clínico San Cecilio
🇪🇸Granada, Spain
Complejo Hospitalario Universitario de Albacete
🇪🇸Albacete, Spain
Hospital Universitari i Poliectenic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Virgen de la Macarena
🇪🇸Sevilla, Spain
Hospital Virgen de la Salud
🇪🇸Toledo, Spain
Hospital Universitario de Galdakao
🇪🇸Galdakao, Bizkaia, Spain
Complexo Hospitalario Universitario de Ourense
🇪🇸Orense, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Sant Joan de Déu de Manresa
🇪🇸Manresa, Barcelona, Spain
Hospital Jerez de la Frontera
🇪🇸Jerez De La Frontera, Cádiz, Spain
Hospital Universitario de Cabueñes
🇪🇸Gijón, Asturias, Spain
Hospital Universitari de Bellvitge
🇪🇸L'Hospitalet De Llobregat, Barcelona, Spain
Hospital de Mataró
🇪🇸Mataró, Barcelona, Spain
Hospital Universitari Son Espases
🇪🇸Palma De Mallorca, Islas Baleares, Spain
Hospital Público General del Tomelloso
🇪🇸Tomelloso, Ciudad Real, Spain
Hospital Universitario Fundación Alcorcón
🇪🇸Alcorcón, Madrid, Spain
Hospital Nuestra Señora del Prado
🇪🇸Talavera De La Reina, Toledo, Spain
Hospital Universitario de Fuenlabrada
🇪🇸Fuenlabrada, Madrid, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Dr. Josep Trueta
🇪🇸Gerona, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Universitario Salamanca
🇪🇸Salamanca, Spain