Safety and Effectiveness Study of Tocilizumab in Patients With Severe COVID-19

NCT ID: NCT04924829

Last Updated: 2021-06-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-06-01

Study Completion Date

2021-08-01

Brief Summary

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

Detailed Description

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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.

Conditions

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Severe COVID 19 Pneumonia Tocilizumab

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Tocilizumab

Group that received tocilizumab (8mg/kg, maximum dose 800 mg, only once) while being admitted with severe COVID-19 pneumonia.

Tocilizumab

Intervention Type DRUG

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

Non-tocilizumab

Group that did not receive tocilizumab but share the same indication according to the elegibility criteria for it as the tocilizumab group while admitted with severe COVID-19 pneumonia.

No interventions assigned to this group

Interventions

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Tocilizumab

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Italiano de Buenos Aires

OTHER

Sponsor Role lead

Responsible Party

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ANACLARA MURUJOSA

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Hospital Italiano de Buenos AIres

Buenos Aires, Buenos Aires F.D., Argentina

Site Status RECRUITING

Countries

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Argentina

Central Contacts

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Anaclara Murujosa, MD

Role: CONTACT

+5491157033547

Diego H Giunta, MD, MPH, PhD

Role: CONTACT

+54 11 4959 0200 ext. 4806

Facility Contacts

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Anaclara Murujosa, MD

Role: primary

+5491157033547

Diego Hernán Giunta, MD, MPH, University SoTL, PhD

Role: backup

+54 11 4959 0200 ext. 4806

References

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Zhang X, Peck R. Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthritis. Expert Rev Clin Pharmacol. 2011 Sep;4(5):539-58. doi: 10.1586/ecp.11.33.

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Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, Machado FR, Lopes RD, Berwanger O, Azevedo LCP, Avezum A, Lisboa TC, Rojas SSO, Coelho JC, Leite RT, Carvalho JC, Andrade LEC, Sandes AF, Pintao MCT, Castro CG Jr, Santos SV, de Almeida TML, Costa AN, Gebara OCE, de Freitas FGR, Pacheco ES, Machado DJB, Martin J, Conceicao FG, Siqueira SRR, Damiani LP, Ishihara LM, Schneider D, de Souza D, Cavalcanti AB, Scheinberg P; Coalition covid-19 Brazil VI Investigators. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021 Jan 20;372:n84. doi: 10.1136/bmj.n84.

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Related Links

Access external resources that provide additional context or updates about the study.

https://covid19.who.int/

WHO Coronavirus (COVID-19) Dashboard

https://doi.org/10.1016/S1473-3099(20)30483-7

A minimal common outcome measure set for COVID-19 clinical research

https://stats.idre.ucla.edu/stata/output/ordered-logistic-regression/

Ordered Logistic Regression \| Stata Annotated Output

https://www.ncbi.nlm.nih.gov/pubmed/2085632

Brant R. Assessing proportionality in the proportional odds model for ordinal logistic regression. Biometrics \[Internet\]. 1990 Dec;46(4):1171-8.

http://dx.doi.org/10.1093/pan/mpl013

Ho DE, Imai K, King G, Stuart EA. Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference \[Internet\]. Vol. 15, Political Analysis. 2007. p. 199-236.

http://dx.doi.org/10.1055/a-1009-6634

Matschinger H, Heider D, König H-H. A Comparison of Matching and Weighting Methods for Causal Inference Based on Routine Health Insurance Data, or: What to do If an RCT is Impossible. Gesundheitswesen \[Internet\]. 2020 Mar;82(S 02):S139-50.

https://www.argentina.gob.ar/sites/default/files/informe-covid-19-n6-tocilizumab.pdf

ACTUALIZACIONES BASADAS EN EVIDENCIA COVID-19 Tocilizumab para el tratamiento de pacientes con COVID-19

Other Identifiers

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6052

Identifier Type: -

Identifier Source: org_study_id

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