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Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study

Trial Profile

Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 14 Apr 2020

At a glance

  • Drugs Tocilizumab (Primary)
  • Indications Adult respiratory distress syndrome; COVID 2019 infections; Cytokine release syndrome; Pneumonia; Severe acute respiratory syndrome
  • Focus Proof of concept; Therapeutic Use
  • Acronyms TOSCA
  • Most Recent Events

    • 14 Apr 2020 Last checked against ClinicalTrials.gov record.
    • 09 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 07 Apr 2020 New trial record

Trial Overview

Purpose

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 Cytokine Release Syndrome.

Primary Endpoints

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.

description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2> 94% for at least 72 hours
time_frame: 14 days

Other Endpoints

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

time_frame: 24 hours

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

description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours
time_frame: 14 days

Duration of hospitalization

description: days
time_frame: 14 days

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

description: days
time_frame: 14 days

Changes from the baseline in the white blood cell count

description: number/microliter
time_frame: 7, 14 days

Changes from the baseline in the lymphocyte populations (cluster of differentiation (CD)3+CD4+, CD3+CD8+, CD19+, Th17)

description: number/microliter
time_frame: 7, 14 days

Changes from the baseline of c-reactive protein (CRP) values

time_frame: 7, 14 days

Changes from the baseline of Ferritin values

time_frame: 7, 14 days

Changes from the baseline of BNP values

time_frame: 7,14 days

Changes from the baseline of CK-MB values

time_frame: 7,14 days

Changes from the baseline of Troponin values

time_frame: 7,14 days

Changes from the baseline of LDH values

time_frame: 7,14 days

Changes from the baseline of myoglobulin values

time_frame: 7,14 days

Changes in myocardial ischemia signs at the electrocardiographic trace (YES or NO)

description: (ST segments elevation or depression, T-wave changes)
time_frame: 7,14 days

Rate of adverse events report during and after tocilizumab

time_frame: 14 days

Mortality (number of Partecipants, cause and timing)

time_frame: 12 weeks

Percentage of patients who develop autoimmune diseases

time_frame: 1 year [1]

Diseases Treated

Indication Qualifiers Patient Segments
Adult respiratory distress syndrome treatment -
COVID 2019 infections treatment -
Cytokine release syndrome treatment -
Pneumonia treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 30

  • Sex male & female
  • Age Group ≥ 18 years; adult

Patient Inclusion Criteria

- 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.

Patient Exclusion Criteria

- 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. - Any condition which, in the opinion of the doctor, precludes the possibility of using the study drug provided for in the RCP. - Any other laboratory condition or parameter that, in the doctor's judgment, precludes the subject's participation in the study.

Trial Details

Identifiers

Identifier Owner
NCT04332913 ClinicalTrials.gov: US National Institutes of Health
0064468-20 -

Trial Dates

  • Initiation Dates

    Planned : 01 Apr 2020

    Actual : 01 Apr 2020

  • Primary Completion Dates

    Planned : 31 Dec 2020

  • End Dates

    Planned : 31 Mar 2021

Other Details

  • Design cohort; observational; prospective
  • Phase of Trial Phase II
  • Location Italy
  • Focus Proof of concept; Therapeutic Use

Interventions

Drugs Route Formulation
TocilizumabPrimary Drug
-
-

Tocilizumab

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Roberto Giacomelli, MD
0862434742 roberto.giacomelli@univaq.it
show details
Ospedale San Salvatore Italy
Roberto Giacomelli, MD, PhD
0039 0862 434742 roberto.giacomelli@univaq.it
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Ospedale San Salvatore L'Aquila Italy
University of L'Aquila
-
-

Trial History

Event Date Event Type Comment
14 Apr 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 14 Apr 2020
09 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 14 Apr 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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