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An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

Trial Profile

An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 16 Apr 2020

At a glance

  • Drugs Tocilizumab (Primary)
  • Indications COVID 2019 infections; Pneumonia; Severe acute respiratory syndrome
  • Focus Therapeutic Use
  • Acronyms TOCI-RE
  • Most Recent Events

    • 09 Apr 2020 New trial record

Trial Overview

Purpose

The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.

Primary Endpoints

Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation

description: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours
time_frame: two weeks from participants' allocation to study arm

Other Endpoints

Death from any cause

description: Death
time_frame: Two weeks from participants' allocation to study arm

Tocilizumab toxicity

description: Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale
time_frame: Two weeks from participants' allocation to study arm

Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment

description: Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment
time_frame: Two weeks from participants' allocation to study arm

Evaluate the progress of the PaO2 / FiO2 ratio

description: Changes from baseline of the PaO2 / FiO2 ratio
time_frame: Two weeks from participants' allocation to study arm

Evaluate the trend over time of the lymphocyte count

description: Changes from baseline of the lymphocyte count
time_frame: Two weeks from participants' allocation to study arm [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 398

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

Patient Inclusion Criteria

- age > 18 years - Informed consent for participation in the study - Real time polymerase chain reaction (PCR) diagnosis of Sars-CoV2 infection - Hospitalization due to clinical / instrumental diagnosis (high resolution chest CT scan or chest x-ray or pulmonary ultrasound) - Presence of acute respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) between 200 and 300 mm/Hg - Presence of exaggerated inflammatory response defined by the presence of at least 1 of the following criteria: - At least one body temperature measurement >38° C in the past two days; - Serum CRP greater than or equal to 10 mg/dl; - CRP increase of at least twice the basal value

Patient Exclusion Criteria

- Patients with respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) <200 mm/Hg or - Patients in non-invasive ventilation or - Patients in invasive ventilation or presence of shock or presence of concomitant organ failure that requires admission to the Intensive Care Unit - Severe heart and kidney failure - Pregnant or breastfeeding patient - Patient who, in the opinion of the clinician or by the patient's express will, will not go to intensive care regardless of the evolution of the lung picture. - Known hypersensitivity to TCZ or its excipients - Patient being treated with immuno-depressors or anti-rejection drugs - Known active infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment - glutamate-pyruvate transaminase (GPT) or glutamine oxaloacetic transaminase (GOT) > 5 times the upper limit of the norm - Neutrophils <500 /mmc - Platelets <50.000 /mmc - Diverticulitis or intestinal perforation - Suspicion of latent tuberculosis

Trial Details

Identifiers

Identifier Owner
NCT04346355 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001386-37 European Clinical Trials Database
RCT-TCZ-COVID19 -

Organisations

  • Affiliations Roche

Trial Dates

  • Initiation Dates

    Actual : 31 Mar 2020

  • Primary Completion Dates

    Planned : 30 May 2020

  • End Dates

    Planned : 30 May 2020

Other Details

  • Design multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Italy
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
TocilizumabPrimary Drug Intravenous Infusion

Control Arm

Standard of care; In the event of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours Drug: Tocilizumab (In case of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours) Other Name: Standard of care

Experimental Arm

Tocilizumab within 8 hours from entering the study + standard of care; 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours Drug: Tocilizumab (In case of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours) Other Name: Standard of care

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Andrea Angheben, M.D. IRCCS Sacro Cuore Don Calabria Italy
Angelo Pan, M.D. ASST Cremona Italy
Carlo Calzetti, M.D. Azienda Ospedaliero-Universitaria Parma Italy
Carlo Salvarani, M.D.
+ 39 0522 295370 carlo.salvarani@ausl.re.it
show details
Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia Italy
Claudio Norbiato, M.D. AO Ordine Mauriziano di Torino Italy
Elisabetta Teopompi, M.D. Ospedale di Guastalla Italy
Elvia Tacconelli Azienda Ospedaliera Universitaria Integrata di Verona Italy
Gianfranco Parati, M.D. IRCCS Istituto Auxologico Italiano Milano Italy
Giovanni Cenderello, M.D. Azienda Sociosanitaria ASL 1 ,Imperia Italy
Giovanni Secondo, M.D. Ospedale Evangelico Internazionale di Genova Italy
Lorenzo Zammarchi, M.D. Azienda Ospedaliero Universitaria Careggi Italy
Lucia Anna C Leone Ospedali Riuniti Padova Sud - ULSS 6 Euganea Italy
Lucio Michieletto, M.D. AULSS 3 Serenissima Ospedale "Dell'Angelo" Italy
Marco Codeluppi, M.D. Azienda Unità Sanitaria Locale di Piacenza Italy
Marco Falcone, M.D. Azienda Ospedaliera Universitaria Pisana Italy
Marco Libanore, M.D: Azienda Ospedaliero Universitaria Ferrara Italy
Marco Massari, M.D. Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia Italy
Mario Salio, M.D. Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo Italy
Massimo Costantini, Ph.D.
+39 0522 295360 massimo.costantini@ausl.re.it
show details
Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia Italy
Paolo Colombelli, M.D. ASST Bergamo Ovest -Treviglio Italy
Pier Giorgio Scotton, M.D. AULSS 2 Marca Trevigiana Italy
Pierferruccio Ballerini, M.D. AULSS2 Marca Trevigiana - Ospedale Vittorio Veneto Italy
Pierpaolo Sainaghi, M.D. Azienda Ospedaliero-Universitaria "Maggiore della Carità" di Novara Italy
Salvatore Casari, M.D. ASST Mantova - Ospedale Carlo Poma Italy
Stefania Artioli, M.D. Azienda Sociosanitaria ASL 5 La Spezia Italy
Valerio Del Bono, M.D. Azienda Ospedaliera S. Croce e Carle Italy

Centres

Centre Name Location Trial Centre Country
AO Ordine Mauriziano di Torino Torino Italy
ASST Bergamo Ovest -Treviglio Treviglio Italy
ASST Cremona Cremona Italy
ASST Mantova - Ospedale Carlo Poma Mantova Italy
AULSS 2 Marca Trevigiana Treviso Italy
AULSS 3 Serenissima Ospedale "Dell'Angelo" Venezia Italy
AULSS2 Marca Trevigiana - Ospedale Vittorio Veneto Treviso Italy
Azienda Ospedaliera S. Croce e Carle Cuneo Italy
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo Alessandria Italy
Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy
Azienda Ospedaliera Universitaria Pisana Pisa Italy
Azienda Ospedaliero Universitaria Careggi Firenze Italy
Azienda Ospedaliero Universitaria Ferrara Ferrara Italy
Azienda Ospedaliero-Universitaria "Maggiore della Carità" di Novara Novara Italy
Azienda Ospedaliero-Universitaria Parma Parma Italy
Azienda Sociosanitaria ASL 1 ,Imperia Imperia Italy
Azienda Sociosanitaria ASL 5 La Spezia La Spezia Italy
Azienda Unità Sanitaria Locale di Piacenza Piacenza Italy
Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia
-
Italy
Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia Reggio Emilia, RE Italy
IRCCS Istituto Auxologico Italiano Milano Milano Italy
IRCCS Sacro Cuore Don Calabria Verona Italy
Ospedale di Guastalla Guastalla, RE Italy
Ospedale Evangelico Internazionale di Genova Genova Italy
Ospedali Riuniti Padova Sud - ULSS 6 Euganea Padova Italy

Trial History

Event Date Event Type Comment
16 Apr 2020 Other trial event New source identified and integrated ClinicalTrials.gov: (US National Institutes of Health: NCT04346355). Updated 16 Apr 2020
09 Apr 2020 New trial record New trial record Updated 09 Apr 2020

References

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

    Available from: URL: http://clinicaltrials.gov
  2. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
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