Clinical Trial to Evaluate the Effectiveness and Safety of Tocilizumab for Treating Patients With COVID-19 Pneumonia

May 31, 2021 updated by: Fundacion SEIMC-GESIDA

A Multicentre, Open-label Clinical Trial to Evaluate the Effectiveness and Safety of Intravenous Tocilizumab for Treating Patients With COVID-19 Pneumonia: the BREATH-19 Study

At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia.

The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an exaggerated immune response. CSS can be triggered by infections or therapeutic interventions, being more severe depending on the degree and duration of immune activation. CSS is as a significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which have been subject to assessment for the treatment of haematological malignancies. Tocilizumab (intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T cell-induced severe or life-threatening CSS.

Based on the experience with tocilizumab in the CSS, and that some patients infected with SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is being investigated in China and Italy, and clinical trials are being conducted/planned in these and several other countries. Real-word experience with tocilizumab IV have shown that in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to normal and respiratory function based on oxygen intake and lung opacities improved remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased in patients infected decreased significantly with tocilizumab, and lymphocytes levels also returned to normal.

All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to initiate the controlled distribution of tocilizumab IV, in light of the increased interest on the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore, tocilizumab might be among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients.

The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU. This large real-world cohort provides a unique opportunity to study a potential medicine during the current emergency situation, and support the findings from the Roche-sponsored Phase III study that is planned to start in early April.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
495

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Albacete, Spain
        • Complejo Hospitalario Universitario de Albacete
      • Badajoz, Spain
        • Hospital Infanta Cristina
      • Barcelona, Spain
        • Hospital De La Santa Creu I Sant Pau
      • Barcelona, Spain
        • Hospital Clinic i Provincial Barcelona
      • Burgos, Spain
        • Hospital Universitario de Burgos
      • Gerona, Spain
        • Hospital Universitario Dr. Josep Trueta
      • Granada, Spain
        • Hospital Universitario Virgen de las Nieves
      • Granada, Spain
        • Hospital Universitario Clínico San Cecilio
      • Madrid, Spain
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain
        • Hospital Universitario Fundacion Jimenez Diaz
      • Madrid, Spain
        • Hospital Universitario Infanta Leonor
      • Madrid, Spain
        • Hospital Universitario HM Sanchinarro
      • Murcia, Spain
        • Hospital Clínico Universitario Virgen de la Arrixaca
      • Málaga, Spain
        • Hospital Regional Universitario de Málaga
      • Orense, Spain
        • Complexo Hospitalario Universitario de Ourense
      • Salamanca, Spain
        • Hospital Universitario Salamanca
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain
        • Hospital Universitario Virgen De La Macarena
      • Toledo, Spain
        • Hospital Virgen de la Salud
      • Valencia, Spain
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitario Dr. Peset
      • Valencia, Spain
        • Hospital Universitari i Poliectenic La Fe
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet
      • Zaragoza, Spain
        • Hospital Clinico Universitario Lozano Blesa
    • Asturias
      • Gijón, Asturias, Spain
        • Hospital Universitario de Cabueñes
    • Barcelona
      • L'Hospitalet De Llobregat, Barcelona, Spain
        • Hospital Universitari de Bellvitge
      • Manresa, Barcelona, Spain
        • Hospital Sant Joan de Déu de Manresa
      • Mataró, Barcelona, Spain
        • Hospital de Mataró
    • Bizkaia
      • Galdakao, Bizkaia, Spain
        • Hospital Universitario de Galdakao
    • Cantabria
      • Santander, Cantabria, Spain
        • Hospital Universitario Marques Valdecilla
    • Ciudad Real
      • Tomelloso, Ciudad Real, Spain
        • Hospital Público General del Tomelloso
    • Cádiz
      • Jerez De La Frontera, Cádiz, Spain
        • Hospital Jerez de la Frontera
    • Islas Baleares
      • Palma De Mallorca, Islas Baleares, Spain
        • Hospital Universitari Son Espases
    • Madrid
      • Alcorcón, Madrid, Spain
        • Hospital Universitario Fundacion Alcorcón
      • Fuenlabrada, Madrid, Spain
        • Hospital Universitario de Fuenlabrada
      • Getafe, Madrid, Spain
        • Hospital Universitario de Getafe
      • Móstoles, Madrid, Spain
        • Hospital Universitario Rey Juan Carlos
      • Móstoles, Madrid, Spain
        • Hospital Rey Juan Carlos
      • San Sebastián De Los Reyes, Madrid, Spain
        • Hospital Universitario Infanta Sofía
    • Navarra
      • Pamplona, Navarra, Spain
        • Complejo Hospitalario de Navarra
    • Toledo
      • Talavera De La Reina, Toledo, Spain
        • Hospital Nuestra Señora del Prado

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Provide oral informed consent to participate in this study.
  • At least 18 years of age.
  • Diagnosed with COVID-19 pneumonia by RT-PCR.
  • Have received the first dose of tocilizumab a maximum of two days before the inclusion or is candidate for tocilizumab treatment
  • Hospitalized or admitted to ICU

Exclusion Criteria:

  • The patient has any other medical condition or is receiving concomitant medication that could, in the opinion of the investigator, compromise the patient's safety or collected data
  • Known severe allergic reactions to tocilizumab or other monoclonal antibodies
  • Active acute and severe infections, including tuberculosis infection
  • Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Tocilizumab

Patients will receive IV tocilizumab as per clinical practice and at the discretion of treating investigator, following the posology indicated in the SmPC, or the recommendations proposed by the Spanish Ministry of Health:

The recommended posology by the SmPC is 8 mg per kg in patients weighing greater than or equal to 30 kg or 12 mg per kg in patients weighing less than 30 kg. If no clinical improvement in the signs and symptoms up to 3 additional doses of tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours.

The recommendations of the Spanish Ministry of Health:

Patients more than 80 kg: first dose 600 mg; second dose 600 mg. Patients less than 80 kg: first dose 600 mg; second dose 400 mg.

A third dose might be considered 16 to 24 hours after if: fever persists or a worsening of the laboratory parameters

Given the exceptionality of the situation modification of doses according to the physician experience will be allowed.
Drug: Tocilizumab
Treatment with Tocilizumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To calulate the time of intubation
Time Frame: through study completion, and average of 1 month
Calculate the mean time of intubation
through study completion, and average of 1 month
To calculate the time with oxygen therapy
Time Frame: through study completion, and average of 1 month
Calculate the mean time with oxygen therapy
through study completion, and average of 1 month
To calculate the time with Non-invasive mechanical ventilation
Time Frame: through study completion, and average of 1 month
Calculate the mean time with Non-invasive mechanical ventilation
through study completion, and average of 1 month
To evaluate mortality rate
Time Frame: through study completion, and average of 1 month
Number of patients deaths of the total of patients included
through study completion, and average of 1 month

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To calculate respiratory function parameters
Time Frame: through study completion, and average of 1 month
To calculate the mean ofPaO2/FiO2
through study completion, and average of 1 month
To calculate respiratory function parameters
Time Frame: through study completion, and average of 1 month
To calculate the mean of levels of oxygen saturation
through study completion, and average of 1 month
To calculate respiratory function parameters
Time Frame: through study completion, and average of 1 month
To calculate the mean of SaO2/FiO2
through study completion, and average of 1 month
To evaluate radiological lung extension
Time Frame: through study completion, and average of 1 month
Evaluate the lung extension of pneumonia
through study completion, and average of 1 month
To evaluate radiological evolution
Time Frame: through study completion, and average of 1 month
Evaluate the type of lung affection
through study completion, and average of 1 month
To describe the duration of hospitalization and ICU use
Time Frame: through study completion, and average of 1 month
Days of hospitalization in survivors and/or days at ICU throughout the study
through study completion, and average of 1 month
To evaluate the requirement of additional organ support
Time Frame: through study completion, and average of 1 month
Percentage of patients with extracorporeal membrane oxygenation
through study completion, and average of 1 month
To evaluate the requirement of additional organ support
Time Frame: through study completion, and average of 1 month
Percentage of patients with molecular adsorbent recirculating system
through study completion, and average of 1 month
To evaluate the requirement of additional organ support
Time Frame: through study completion, and average of 1 month
Percentage of patients with dialysis
through study completion, and average of 1 month
To evaluate the requirement of additional organ support
Time Frame: through study completion, and average of 1 month
Percentage of patients with other support therapy
through study completion, and average of 1 month
To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers
Time Frame: through study completion, and average of 1 month
Analyze the levels of IL-6
through study completion, and average of 1 month
To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab
Time Frame: through study completion, and average of 1 month
Incidence of adverse events
through study completion, and average of 1 month
To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab
Time Frame: through study completion, and average of 1 month
Incidence of adverse events by dose of Tocilizumab
through study completion, and average of 1 month
To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity
Time Frame: through study completion, and average of 1 month
To evaluate the time to RT-PCR virus negativity
through study completion, and average of 1 month
To evaluate the effect of IV tocilizumab on the serum levels of inflammatory
Time Frame: through study completion, and average of 1 month
Analyze the levels of CRP
through study completion, and average of 1 month
To evaluate the effect of IV tocilizumab on the serum levels of inflammatory
Time Frame: through study completion, and average of 1 month
Analyze the levels of procalcitonin (PCT)
through study completion, and average of 1 month
To evaluate the effect of IV tocilizumab on the serum levels of inflammatory
Time Frame: through study completion, and average of 1 month
Analyze the levels of ID-dimer
through study completion, and average of 1 month
To evaluate the effect of IV tocilizumab on the serum levels of inflammatory
Time Frame: through study completion, and average of 1 month
Analyze the levels of ferritin
through study completion, and average of 1 month
To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab
Time Frame: through study completion, and average of 1 month
Indicende of serious adverse events
through study completion, and average of 1 month
To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab
Time Frame: through study completion, and average of 1 month
Indicende of serious adverse events based on dose of Tocilizumab
through study completion, and average of 1 month
To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab
Time Frame: through study completion, and average of 1 month
Indicende of adverse events of special interest based on dose of Tocilizumab
through study completion, and average of 1 month
To evaluate mortality rate
Time Frame: through study completion, and average of 1 month
Number of patients deaths of the total of patients included based on dose of Tocilizumab
through study completion, and average of 1 month
To evaluate respiratory function
Time Frame: through study completion, and average of 1 month
Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab
through study completion, and average of 1 month
To evaluate mortality rate
Time Frame: through study completion, and average of 1 month
Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment
through study completion, and average of 1 month
To evaluate mortality rate
Time Frame: through study completion, and average of 1 month
Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment
through study completion, and average of 1 month
To evaluate respiratory function
Time Frame: through study completion, and average of 1 month
Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment
through study completion, and average of 1 month
To evaluate respiratory function
Time Frame: through study completion, and average of 1 month
Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment
through study completion, and average of 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundacion SEIMC-GESIDA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG
Dynamic Science S.L.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jose Antonio Pérez Molina, Hospital Universitario Ramon y Cajal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 22, 2020

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 23, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 23, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 13, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BREATH-19 (FSG011-20)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID-19

Clinical Trials on Tocilizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings