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Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

Primary Purpose

COVID-19 Pneumonia

Status

Terminated

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Tocilizumab

About this trial

This is an interventional treatment trial for COVID-19 Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Experimental Arm

Control Arm

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

Death from any cause

Death

Tocilizumab toxicity

Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale

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

Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment

Evaluate the progress of the PaO2 / FiO2 ratio

Changes from baseline of the PaO2 / FiO2 ratio

Evaluate the trend over time of the lymphocyte count

Changes from baseline of the lymphocyte count

Full Information

NCT ID

NCT04346355

First Posted

April 12, 2020

Last Updated

June 18, 2020

Sponsor

Azienda Unità Sanitaria Locale Reggio Emilia

1. Study Identification

Unique Protocol Identification Number

NCT04346355

Brief Title

Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Terminated

Why Stopped

Based on interim analysis for futility and given an enrolment rate almost nil

Study Start Date

March 31, 2020 (Actual)

Primary Completion Date

June 6, 2020 (Actual)

Study Completion Date

June 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Azienda Unità Sanitaria Locale Reggio Emilia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19 Pneumonia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

126 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Arm

Arm Type

Experimental

Arm Description

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

Arm Title

Control Arm

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tocilizumab

Other Intervention Name(s)

Standard of care

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

two weeks from participants' allocation to study arm

Secondary Outcome Measure Information:

Title

Death from any cause

Description

Death

Time Frame