E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 pneumonia |
Neumonía por COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
COVID-19 pneumonia |
Neumonía por COVID-19 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia. Improvement of respiratory function based on: - Time to intubation (if not previously intubated) and duration of intubation. - Time of non-invasive mechanical ventilation. - Time of oxygen therapy.
Mortality rate |
Evaluar la efectividad del tocilizumab IV en el tratamiento de pacientes con neumonía por COVID-19. La mejora de la función respiratoria basada en: - Tiempo de intubación (si no se intubó previamente) y duración de la intubación. - Tiempo de ventilación mecánica no invasiva (VMNI). - Tiempo de oxigenoterapia.
Tasa de mortalidad |
|
E.2.2 | Secondary objectives of the trial |
- To describe oxygen saturation (SpO2), PaO2/FiO2 (<300), or the equivalent SaO2/FiO2 (<315) - To evaluate radiological evolution - To describe the duration of hospitalization and/or ICU stay - To evaluate the requirement of additional organ support, including kidney dialysis, molecular adsorbent recirculating system (MARS), extracorporeal membrane oxygenation (ECMO), or other - To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers - To describe safety of IV tocilizumab in patients with COVID-19 pneumonia - To identify prognosis factors of IV tocilizumab effectiveness related to inflammatory markers and clinical/radiological features. - To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity, as appropriate. - To compare the effectiveness and safety outcomes based on the different doses of IV tocilizumab used in the participating centres. - To identify patient profile suitable to be benefited with tocilizumab |
- Describir la saturación de oxígeno (SpO2), PaO2 / FiO2 (<300) o el equivalente de SaO2 / FiO2 (<315) - Evaluar la evolución radiológica - Describir la duración de la hospitalización y / o la estancia en la UCI - Evaluar la necesidad de soporte orgánico adicional, incluyendo diálisis de riñón, diálisis de hígado usando MARS, OMECu otras - Evaluar el efecto de tocilizumab sobre los niveles séricos de marcadores inflamatorios - Describir la seguridad de tocilizumab - Identificar los factores pronósticos de la efectividad de tocilizumab relacionados con marcadores inflamatorios y características clínicas / radiológicas. - Evaluar el tiempo hasta la aparición de resultado negativo del virus a través de la RT-PCR, según corresponda. - Comparar los resultados de efectividad y seguridad basados en las diferentes dosis de tocilizumab utilizadas en los centros participantes. - Identificar el perfil de paciente que se pueda beneficiar del tratamiento con tocilizumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
- Proporcionar consentimiento informado oral para participar en este estudio. - Al menos 18 años de edad. - Diagnosticado con neumonía por COVID-19 por RT-PCR. - Haber recibido la primera dosis de tocilizumab un máximo de dos días antes de la inclusión o ser candidato para el tratamiento con tocilizumab. - Hospitalizado o ingresado en la UCI |
|
E.4 | Principal 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 |
- El paciente tiene cualquier otra afección médica o está recibiendo medicación concomitante que podría, en opinión del investigador, comprometer la seguridad del paciente o los datos obtenidos. - Reacciones alérgicas graves conocidas a tocilizumab u otros anticuerpos monoclonales. - Infecciones agudas y graves activas, incluida la infección tuberculosa. - Embarazada o lactante, o prueba de embarazo positiva en un examen previo a la dosis. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Respiratory function, defined as: Start date of intubation (in patients not previously initiated). Date of extubation. Start date of NIMV and date of independence from NIMV (duration of NIMV). Start date of oxygen therapy and date of independence from oxygen therapy (duration of oxygen therapy).
- Mortality rate. |
- Función respiratoria, definida como: Fecha de inicio de la intubación (en pacientes no iniciados previamente). Fecha de extubación. Fecha de inicio de VMNI y fecha de independencia de VMNI (duración de VMNI). Fecha de inicio de la oxigenoterapia y fecha de independencia de la oxigenoterapia (duración de la oxigenoterapia).
- Tasa de mortalidad. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End points will be evaluated on a ongoing basis during the clinical trial |
Las variables serán evaluadas forma continua durante el ensayo clínico |
|
E.5.2 | Secondary end point(s) |
- Levels of oxygen saturation (SpO2), PaO2/FiO2 (<300), or the equivalent SaO2/FiO2 (<315) at 1 day after the first dose and every 3 days during the hospitalization. - Results from the chest x-ray/computed tomography (CT) scan, including extension of lung affection (unilobar or multilobar, unilateral or bilateral, diffuse) and type (opacities, interstitial infiltrates, pneumothorax, pleural effusion) obtained (when available) throughout the study. - Days of hospitalization in survivors and/or days at ICU throughout the study. - Need of additional organ support, including kidney dialysis, MARS, ECMO, or other throughout the study. - Levels of IL-6, CRP, procalcitonin (PCT), D-dimer and ferritin (when available) throughout the study. - Adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), vital signs, physical examinations, and concomitant medication use over time. - Association between the abovementioned clinical and radiological features and IV tocilizumab effectiveness. - Time to RT-PCR virus negativity, as appropriate. - Respiratory function and adverse events using different doses of tocilizumab in the participating centres. - Categorization of the different parameters of effectiveness and its relation with different factors related to the study treatment, disease status and demographic and clinical factors |
- Niveles de saturación de oxígeno (SpO2), PaO2 / FiO2 (<300), o el equivalente de SaO2 / FiO2 (<315) 1 día después de la primera dosis y cada 3 días durante la hospitalización. - Resultados de la radiografía de tórax/escáner de Tomografía computarizada (TC), incluyendo la extensión de la afección pulmonar (unilobular o multilobular, unilateral o bilateral, difusa) y tipo (opacidades, infiltrados intersticiales, neumotórax, derrame pleural), obtenidos (cuando estén disponibles) durante todo el estudio. - Días de hospitalización en supervivientes y / o días en la UCI durante todo el estudio. - Necesidad de soporte orgánico adicional, incluyendo diálisis de riñón, diálisis de hígado usando MARS (Molecular Adsorbents Recirculation System), oxigenación por membrana extracorpórea (OMEC), u otras durante todo el estudio. - Niveles de IL-6, proteína C reactiva (PCR), procalcitonina (PCT), dímero D y ferritina (cuando estén disponibles) durante todo el estudio. - Acontecimientos adversos (AA), acontecimientos adversos graves, acontecimientos adversos de especial interés, signos vitales, exámenes físicos y el uso concomitante de medicamentos con el tiempo. - Asociación entre las características clínicas y radiológicas mencionadas anteriormente y la efectividad de tocilizumab. - Tiempo hasta la negatividad del virus por RT-PCR, según corresponda. - Función respiratoria y acontecimientos adversos usando diferentes dosis de tocilizumab en los centros participantes. - Categorización de los diferentes parámetros de efectividad y su relación con diferentes factores relacionados con el tratamiento del estudio, el estado de la enfermedad y los factores demográficos y clínicos |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End points will be evaluated on a ongoing basis during the clinical trial |
Las variables serán evaluadas forma continua durante el ensayo clínico |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 42 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LVLS |
Ultima visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |