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

NCT04924829 | Unknown

• 1 other identifier: 6052
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Severe COVID 19 Pneumonia; Tocilizumab

Keywords

covid 19; tocilizumab; severe pneumonia

Outcome Measures

Primary Outcomes (3)

• 28-day mortality

  28-day mortality

  28 days from hospital admission

• Percentage of patients in invasive mechanical ventilation at day 28

  Percentage of patients that received invasive mechanical ventilation at day 28 following hospital admission.

  28 days from hospital admission

• Clinical status during follow-up at 28th day

  Ordinal outcome with seven mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) Discharged or ready for discharge; (2) Admitted to non-ICU ward without oxygen; (3) admitted to non-ICU ward but requiring supplemental oxygen; (4) admitted to ICU or non ICU ward requiring high flow nasal canula or other non invasive mechanical ventilation; (5) admitted to ICU ward requiring invasive mechanical ventilation (6) admitted to ICU ward requiring extracorporeal membrane oxygenation or invasive mechanical ventilation plus other vital organ support; (7) death

  28th day from hospital admission

Secondary Outcomes (12)

• Mortality rate

  Days 14 and 21

• Percentage of patients in invasive mechanical ventilation at day 14 and 21

  Days 14 and 21

• Percentage of patients with hospital discharge at day 7, 14, 21 and 28

  Days 7, 14, 21 and 28

• Time to hospital discharge

  Up to 60 days

• Percentage of patients admitted to ICU-ward at day 28

  28th day from hospital admission

Study Arms (2)

Tocilizumab

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

Drug: Tocilizumab

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.

Interventions

Tocilizumab DRUG

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

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (1)

Hospital Italiano de Buenos AIres

Buenos Aires, Buenos Aires F.D., 1199, Argentina

RECRUITING

Related Publications (15)

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• Zhu J, Pang J, Ji P, Zhong Z, Li H, Li B, Zhang J. Elevated interleukin-6 is associated with severity of COVID-19: A meta-analysis. J Med Virol. 2021 Jan;93(1):35-37. doi: 10.1002/jmv.26085. Epub 2020 Oct 30. No abstract available.

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• REMAP-CAP Investigators; Gordon AC, Mouncey PR, Al-Beidh F, Rowan KM, Nichol AD, Arabi YM, Annane D, Beane A, van Bentum-Puijk W, Berry LR, Bhimani Z, Bonten MJM, Bradbury CA, Brunkhorst FM, Buzgau A, Cheng AC, Detry MA, Duffy EJ, Estcourt LJ, Fitzgerald M, Goossens H, Haniffa R, Higgins AM, Hills TE, Horvat CM, Lamontagne F, Lawler PR, Leavis HL, Linstrum KM, Litton E, Lorenzi E, Marshall JC, Mayr FB, McAuley DF, McGlothlin A, McGuinness SP, McVerry BJ, Montgomery SK, Morpeth SC, Murthy S, Orr K, Parke RL, Parker JC, Patanwala AE, Pettila V, Rademaker E, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Sligl WI, Turgeon AF, Turner AM, van de Veerdonk FL, Zarychanski R, Green C, Lewis RJ, Angus DC, McArthur CJ, Berry S, Webb SA, Derde LPG. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021 Apr 22;384(16):1491-1502. doi: 10.1056/NEJMoa2100433. Epub 2021 Feb 25.

  PMID: 33631065 BACKGROUND

• Angriman F, Ferreyro BL, Burry L, Fan E, Ferguson ND, Husain S, Keshavjee SH, Lupia E, Munshi L, Renzi S, Ubaldo OGV, Rochwerg B, Del Sorbo L. Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context. Lancet Respir Med. 2021 Jun;9(6):655-664. doi: 10.1016/S2213-2600(21)00139-9. Epub 2021 Apr 27.

  PMID: 33930329 BACKGROUND

• McCreary EK, Angus DC. Efficacy of Remdesivir in COVID-19. JAMA. 2020 Sep 15;324(11):1041-1042. doi: 10.1001/jama.2020.16337. No abstract available.

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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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• Pons S, Fodil S, Azoulay E, Zafrani L. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Crit Care. 2020 Jun 16;24(1):353. doi: 10.1186/s13054-020-03062-7.

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• Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):32-40. doi: 10.1001/jamainternmed.2020.6820.

  PMID: 33080017 BACKGROUND

• Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, Bruzzi P, Boni F, Braglia L, Turra C, Ballerini PF, Sciascia R, Zammarchi L, Para O, Scotton PG, Inojosa WO, Ravagnani V, Salerno ND, Sainaghi PP, Brignone A, Codeluppi M, Teopompi E, Milesi M, Bertomoro P, Claudio N, Salio M, Falcone M, Cenderello G, Donghi L, Del Bono V, Colombelli PL, Angheben A, Passaro A, Secondo G, Pascale R, Piazza I, Facciolongo N, Costantini M; RCT-TCZ-COVID-19 Study Group. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):24-31. doi: 10.1001/jamainternmed.2020.6615.

  PMID: 33080005 BACKGROUND

• 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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• Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, Criner GJ, Kaplan-Lewis E, Baden R, Pandit L, Cameron ML, Garcia-Diaz J, Chavez V, Mekebeb-Reuter M, Lima de Menezes F, Shah R, Gonzalez-Lara MF, Assman B, Freedman J, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. Epub 2020 Dec 17.

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Related Links

• WHO Coronavirus (COVID-19) Dashboard
• A minimal common outcome measure set for COVID-19 clinical research
• Ordered Logistic Regression \| Stata Annotated Output
• Brant R. Assessing proportionality in the proportional odds model for ordinal logistic regression. Biometrics \[Internet\]. 1990 Dec;46(4):1171-8.
• 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.
• 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.
• ACTUALIZACIONES BASADAS EN EVIDENCIA COVID-19 Tocilizumab para el tratamiento de pacientes con COVID-19
• IDS COVID 19 guideline treatment and management

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Anaclara Murujosa, MD

CONTACT

+5491157033547; anaclara.murujosa@hospitalitaliano.org.ar

Diego H Giunta, MD, MPH, PhD

CONTACT

+54 11 4959 0200; diego.giunta@hospitalitaliano.org.ar

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: June 14, 2021
• Study Start: June 1, 2021
• Primary Completion: July 1, 2021
• Study Completion: August 1, 2021
• Last Updated: June 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)