Efficacy and Safety of Tocilizumab in the Treatment of SARS-Cov-2 Related Pneumonia

Last updated: April 9, 2020
Sponsor: University of L'Aquila
Overall Status: Active - Recruiting

Phase

N/A

Condition

Pneumonia

Covid-19

Corona Virus

Treatment

N/A

Clinical Study ID

NCT04332913
0064468/20
  • Ages > 18
  • All Genders

Study Summary

The current spread of the COrona VIrus Disease-2019 (COVID-19) epidemic in Italy, and the current lack of effective and approved drugs for its treatment, poses the problem of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients management, especially those who underwent to experience COVID-19 complications, such as CRS. This unmet need becomes more severe if the investigator consider that, the COVID-19 mortality stands around 2% in the general population, but it rises to 49% when considering intensive care unit (ICU) patients. To increase the chances of survival of these patients, the compassionate use of the available drugs is required, based on literature data, to the best of our abilities. ICU patients with cytokine release syndrome (CRS) secondary to COVID-19, show increased production of pro-inflammatory cytokines, including interleukin (IL-6), IL-2, IL-7, IL-10, tumor necrosis factor (TNF)-α and interferon (INF)γ, similar to that found in patients who develop CRS secondary to Chimeric Antigen Receptor-T (CAR-T) therapy. Although immuno-modulatory therapy is not routinely recommended in COVID-19 pneumonia, tocilizumab might have a rationale in those patients who develop CRS, blocking the complications caused by high levels of IL-6, and possibly preventing the development of a multi-organ failure. Reassuring data in this sense, come from the first studies conducted in China. In a Chinese pilot study, Xiaoling Xu and collaborators used tocilizumab (at a dosage of 400 mg iv in a single dose, with a possible second dose in case of no clinical response) in patients with COVID-19 in the presence of one of the following criteria: i) respiratory rate ≥ 30 acts/min; ii) SpO2 ≤ 93% in ambient air; iii) PaO2/FiO2 ≤ 300 mmHg. In the 21 patients treated with tocilizumab a significant reduction in IL-6 levels and fever, with improvement in lung function, was demonstrated. Besides, 90% of treated patients showed an improvement in the radiological picture, in terms of a decrease in the frosted glass areas, and a return to normal lymphocytes count in the peripheral blood. This is a prospective observational clinical study and it is aimed at verifying tocilizumab efficacy and safety in patients with COVID-19 complicated by acute distress respiratory syndrome (ARDS) and CRS.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • All gender patients aged ≥ 18 years;

  • Patients with SARS-CoV-2 infection confirmed by tests (RT-PCR) and pulmonaryinvolvement, hospitalized, at the end of the initial phase of high viral load ofCOVID-19 (apyretic> 72 hours and / or at least 7 days after onset of symptoms);

  • Worsening of respiratory exchanges such as to require non-invasive or invasiveventilation support (BCRSS score ≥ 3).

  • High levels of IL-6 (> 40 pg/mL) or alternatively CRP and/or ferritin and/or D-dimerand/or fibrinogen values higher than the reference values or rapidly increasing;

  • Signature of informed consent.

Exclusion

Exclusion Criteria:

  • Alanine aminotransferase and/or Aspartate aminotransferase (ALT / AST) > 5 timescompared to normal laboratory values.

  • Presence of a chronic renal failure ≥ 4 stage (glomerular filtrate values <30ml/min/1.73 m2).

  • Presence of neutropenia (neutrophils count < 500 / mm3).

  • Platelet count less than 50 x 103/μL.

  • Documented sepsis from other pathogens other than SARS-CoV-2.

  • Presence of co-morbidities associated, in clinical judgment, with an unfavourableoutcome.

  • Complicated diverticulitis and / or intestinal perforation.

  • Skin infection in progress (e.g. dermohypodermitis not controlled by antibiotictherapy).

  • Immuno-suppressive anti-rejection therapy.

  • Pregnancy or woman of childbearing age who does not use contraceptive and/orbreastfeeding measures.

  • Previous ischemic attack or myocardial infarction.

  • NYHA class III or IV heart failure.

  • Severe depressive syndrome or other psychiatric disease which, in the opinion of thedoctor, can preclude patient participation in the study.

  • Presence of known malignant neoplasms.

  • Clinically significant history of alcohol abuse or drug addiction which, in theopinion of the doctor, may preclude the subject's participation in the study.

  • Any condition which, in the opinion of the doctor, precludes the possibility of usingthe study drug provided for in the RCP.

  • Any other laboratory condition or parameter that, in the doctor's judgment, precludesthe subject's participation in the study.

Study Design

Total Participants: 30
Study Start date:
April 01, 2020
Estimated Completion Date:
March 31, 2021

Connect with a study center

  • Ospedale San Salvatore

    L'Aquila, 67100
    Italy

    Active - Recruiting

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