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

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ClinicalTrials.gov Identifier: NCT04924829
Recruitment Status : Recruiting
First Posted : June 14, 2021
Last Update Posted : June 14, 2021
Sponsor:
Information provided by (Responsible Party):
ANACLARA MURUJOSA, Hospital Italiano de Buenos Aires

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

Condition or disease Intervention/treatment
Severe COVID 19 Pneumonia Tocilizumab Drug: Tocilizumab

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.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Safety and Effectiveness Observational Study of Anti IL-6 Tocilizumab in Hospital Admitted Patients With Severe COVID-19 Pneumonia.
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : August 1, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

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

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.



Primary Outcome Measures :
  1. 28-day mortality [ Time Frame: 28 days from hospital admission ]
    28-day mortality

  2. Percentage of patients in invasive mechanical ventilation at day 28 [ Time Frame: 28 days from hospital admission ]
    Percentage of patients that received invasive mechanical ventilation at day 28 following hospital admission.

  3. Clinical status during follow-up at 28th day [ Time Frame: 28th day from hospital admission ]
    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


Secondary Outcome Measures :
  1. Mortality rate [ Time Frame: Days 14 and 21 ]
  2. Percentage of patients in invasive mechanical ventilation at day 14 and 21 [ Time Frame: Days 14 and 21 ]
  3. Percentage of patients with hospital discharge at day 7, 14, 21 and 28 [ Time Frame: Days 7, 14, 21 and 28 ]
  4. Time to hospital discharge [ Time Frame: Up to 60 days ]
    Time from hospital admission to hospital discharge

  5. Percentage of patients admitted to ICU-ward at day 28 [ Time Frame: 28th day from hospital admission ]
    Percentage of patients admitted to ICU-ward at day 28 from hospital admission

  6. Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status [ Time Frame: Up to 60 days ]
  7. Percentage of patients with need of tracheostomy at day 28 of hospital admission [ Time Frame: 28th day from hospital admission ]
  8. Time to mechanical ventilation from hospital admission [ Time Frame: Up to 28 days ]
  9. Days of ICU admission [ Time Frame: Up to 60 days ]
  10. Time to ICU discharge from hospital admission [ Time Frame: Up to 60 days ]
    Time to ICU discharge from hospital admission in the patients subgroup that required ICU admission.

  11. Percentage of patients with adverse effects / serious adverse effects [ Time Frame: Up to 28 days ]
  12. Percentage of superimposed infections [ Time Frame: 28th day from hospital admission ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04924829


Contacts
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Contact: Anaclara Murujosa, MD +5491157033547 anaclara.murujosa@hospitalitaliano.org.ar
Contact: Diego H Giunta, MD, MPH, PhD +54 11 4959 0200 ext 4806 diego.giunta@hospitalitaliano.org.ar

Locations
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Argentina
Hospital Italiano de Buenos AIres Recruiting
Ciudad autónoma de Buenos Aires, Caba, Argentina, 1199
Contact: Anaclara Murujosa, MD    +5491157033547    anaclara.murujosa@hospitalitaliano.org.ar   
Contact: Diego Hernán Giunta, MD, MPH, University SoTL, PhD    +54 11 4959 0200 ext 4806    diego.giunta@hospitalitaliano.org.ar   
Sponsors and Collaborators
Hospital Italiano de Buenos Aires
Additional Information:

Publications:
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, Pettilä 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.

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Responsible Party: ANACLARA MURUJOSA, MD, Hospital Italiano de Buenos Aires
ClinicalTrials.gov Identifier: NCT04924829    
Other Study ID Numbers: 6052
First Posted: June 14, 2021    Key Record Dates
Last Update Posted: June 14, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ANACLARA MURUJOSA, Hospital Italiano de Buenos Aires:
covid 19
tocilizumab
severe pneumonia
Additional relevant MeSH terms:
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COVID-19
Pneumonia
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases