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

NCT04332913 | Unknown

• 1 other identifier: 0064468/20
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COVID-19 Pneumonia

Keywords

Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with complete recovery defined as fever disappearance and return to normal peripheral oxygen saturation values (SpO2) after 14 days from the end of treatment with tocilizumab.

  Fever normalization criteria: Temperature \<36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2\> 94% for at least 72 hours

  14 days

Secondary Outcomes (17)

• Percentage of patients achieving a score <3 on the Brescia-COVID respiratory severity scale (BCRSS) after the last tocilizumab administration.

  24 hours

• Percentage of patients with partial recovery defined as the disappearance of fever 14 days after the end of treatment with tocilizumab.

  14 days

• Duration of hospitalization

  14 days

• Time to the first negative SARS-CoV-2 negative RT-PCR test

  14 days

• Changes from the baseline in the white blood cell count

  7, 14 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

COVID-19 patients with pneumonia requiring hospitalization

You may qualify if:

• All gender patients aged ≥ 18 years;
• Patients with SARS-CoV-2 infection confirmed by tests (RT-PCR) and pulmonary involvement, hospitalized, at the end of the initial phase of high viral load of COVID-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 invasive ventilation support (BCRSS score ≥ 3).
• High levels of IL-6 (\> 40 pg/mL) or alternatively CRP and/or ferritin and/or D-dimer and/or fibrinogen values higher than the reference values or rapidly increasing;
• Signature of informed consent.

You may not qualify if:

• Alanine aminotransferase and/or Aspartate aminotransferase (ALT / AST) \> 5 times compared to normal laboratory values.
• Presence of a chronic renal failure ≥ 4 stage (glomerular filtrate values \<30 ml/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 unfavourable outcome.
• Complicated diverticulitis and / or intestinal perforation.
• Skin infection in progress (e.g. dermohypodermitis not controlled by antibiotic therapy).
• Immuno-suppressive anti-rejection therapy.
• Pregnancy or woman of childbearing age who does not use contraceptive and/or breastfeeding 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 the doctor, can preclude patient participation in the study.
• Presence of known malignant neoplasms.
• Clinically significant history of alcohol abuse or drug addiction which, in the opinion of the doctor, may preclude the subject's participation in the study.

Sponsors & Collaborators

• University of L'Aquila: lead

Study Sites (1)

Ospedale San Salvatore

L’Aquila, 67100, Italy

RECRUITING

Related Publications (15)

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  RESULT

Central Study Contacts

Roberto Giacomelli, MD, PhD

CONTACT

0039 0862 434742; roberto.giacomelli@univaq.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: April 3, 2020
• Study Start: April 1, 2020
• Primary Completion: December 31, 2020
• Study Completion: March 31, 2021
• Last Updated: April 13, 2020

Record last verified: 2020-04

Locations

IT (1)