Clinical trial NCT04924829: Safety and Effectiveness Study of Tocilizumab in Patients With Severe COVID-19
Official title: Safety and Effectiveness Observational Study of Anti IL-6 Tocilizumab in Hospital Admitted Patients With Severe COVID-19 Pneumonia.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Severe COVID 19 Pneumonia
Tocilizumab
Keywords: covid 19
tocilizumab
severe pneumonia
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
First posted: 2021-06-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to hospital with severe COVID-19 pneumonia that have progressed in the requirement of oxygen or need of non-rebreathing mask that have an active inflammatory state defined as persistent fever, CRP over 50 mg/dL or D dimer over 1000 ng/dL.

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 28-day mortality
timeFrame: 28 days from hospital admission
measure: Percentage of patients in invasive mechanical ventilation at day 28
timeFrame: 28 days from hospital admission
measure: Clinical status during follow-up at 28th day
timeFrame: 28th day from hospital admission
Secondary outcomes:
measure: Mortality rate
timeFrame: Days 14 and 21
measure: Percentage of patients in invasive mechanical ventilation at day 14 and 21
timeFrame: Days 14 and 21
measure: Percentage of patients with hospital discharge at day 7, 14, 21 and 28
timeFrame: Days 7, 14, 21 and 28
measure: Time to hospital discharge
timeFrame: Up to 60 days
measure: Percentage of patients admitted to ICU-ward at day 28
timeFrame: 28th day from hospital admission
measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status
timeFrame: Up to 60 days
measure: Percentage of patients with need of tracheostomy at day 28 of hospital admission
timeFrame: 28th day from hospital admission
measure: Time to mechanical ventilation from hospital admission
timeFrame: Up to 28 days
measure: Days of ICU admission
timeFrame: Up to 60 days
measure: Time to ICU discharge from hospital admission
timeFrame: Up to 60 days
measure: Percentage of patients with adverse effects / serious adverse effects
timeFrame: Up to 28 days
measure: Percentage of superimposed infections
timeFrame: 28th day from hospital admission
Other outcomes:
Locations:
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos AIres
state: Caba
Study officials:
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