Resumen

Retrospective observational cohort study to evaluate the safety and effectiveness of tocilizumab in the treatment of severe COVID-19 pneumonia

Descripción detallada

Since the appearence of the disease today known as COVID-19 there has been multiple interventions to try to gain knowledge on the subject and obtain a benefitial effect treating this condition. Tocilizumab, a monoclonal antibody targeting IL-6 receptor has arised as an alternative for the treament of COVID-19 pneumonia. It is a drug used for the treatment of rhemautoid arthritis and other autoimmune diseases as well as approved in recent years for the treatment of the cytokine release syndrome (CRS) in CAR-T therapy. It is based in this last premise that the benefitial effect on COVID-19 pneumonia has been sought of. According to investigation into the physiopathology of the virus, it is supposed to trigger the inflamattory cascade that generates damage to lungs and creates the most severe cases of the disease. These findings could imply that tocilizumab may serve to interrupt this cytokine storm and prevent the progression of the disease. The aim of the study is to evaluate the effectiveness and safety of tocilizumab in the treatment of severe cases of COVID-19. For that purpose, an observational retrospective cohort study has been designed comparing two populations that share the same indication for the treatment with tocilizumab. One having received the drug and the other in a close previous period of time that has not received it because of lack of availability or generalisation of its use. Mortality will be assesed as well as other variables such as need for mechanical ventilation and adverse effects of tocilizumab.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Hospital admitted patients with severe COVID-19 pneumonia (Individuals who have SpO2 \<94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) \<300 mm Hg, respiratory frequency \>30 breaths/min, or lung infiltrates \>50%).
Confirmed diagnosis of Covid-19 through qualitative polymerase-reverse transcriptase (qRT-PCR -GeneDX Co, Ltd o similar) or antigen rapid test.
Patients who received tocilizumab or shared the same indication but did not received it (same period of time or previous close period) that:
Progress in the requirement of supplemental oxygen (over 3L/m) and/or use of non-rebreathing mask with 8L/m or more to mantain a Sp02\>= 94%.
AND
\* Active inflammatory state defined as persistent fever \> 38°C (defined as 2 or more measurements in a 24-hour period from hospital admission) despite the use of dexamethasone in the previous 48 hours OR C reactive Protein \> 50 mg /dL OR D Dimer \> 1000 ng/mL.

Criterios de exclusión

Asymptomatic, mild or moderate COVID-19 disease.
Patients with some type of immunosupression (HIV, use of immunomodulatory drugs, organ-trasplant receipt patients)
Pregnant or breast-feeding
Patients with augmented risk of bowel perforation (history of diverticulitis or bowel surgery in the three months prior to the study entrance date)
Known severe allergic reactions to TCZ
Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 x upper limit of normal (ULN) at screening
Absolute neutrophil count (ANC) \< 1000/mL at screening
Platelet count \< 50,000/mL at screening
Positive Hepatitis B Surface (HbS) antigen
Procalcitonine \> 0,5 ng/mL
Day of symptom onset before day 7 or after day 12
Patients with dementia
Patients non eligible to progress to mechanical ventilation because of frailty/comorbidites according to medical decision.

Intervenciones

drug

Tocilizumab

Tocilizumab received as a single intravenous infusion over the period of 60 minutes. Dose of 8 mg/kg, maximum dose of 800 mg.

Ubicaciones

Hospital Italiano de Buenos AIres

Buenos Aires, Buenos Aires F.D., Argentina

Anaclara Murujosa, MD · anaclara.murujosa@hospitalitaliano.org.ar · +5491157033547

RECRUITING

Patrocinadores

PrincipalHospital Italiano de Buenos Aires

Contactos

Anaclara Murujosa, MD

CONTACT

anaclara.murujosa@hospitalitaliano.org.ar +5491157033547

Diego H Giunta, MD, MPH, PhD