Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 With Inflammatory Markers (TOCIBRAS)

August 22, 2020 updated by: Dr Rozana Mesquita Ciconelli, Beneficência Portuguesa de São Paulo

Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 and Increased Inflammatory Markers: a Phase III Randomized Clinical Trial (COVID-19 Coalition Brazil VI) (TOCIBRAS)

The trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.

Study Overview

Status

Status

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

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

Coalition VI (TOCIBRÁS) is a prospective phase III randomized controlled trial that evaluates the efficacy and safety of Tocilizumab, an antibody anti-IL-6 receptor in patients with moderate to severe COVID-19 with increased inflammatory markers. This is a superiority open-label study with two arms. The control arm receives the best supportive care, and the experimental receives it plus tocilizumab. Randomization is done centrally by REDCap 1:1. Patients will be followed until Day 29 after randomization.

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.
129

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 3

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

  • Brazil
      • Sao Paulo, Brazil, 01323001
        • HAOC - Hospital Alemão Oswaldo Cruz
      • Sao Paulo, Brazil, 01323900
        • Beneficencia Portuguesa de Sao Paulo
      • Sao Paulo, Brazil
        • HAOC - Hospital Alemao Oswaldo Cruz - unidade Vergueiro
      • Sao Paulo, Brazil
        • HIAE - Hospital Israelita Albert Einstein
      • Sao Paulo, Brazil
        • HSL - Hospital Sírio Libanês
    • SP
      • Sao Paulo, SP, Brazil, 04004030
        • HCOR -Hospital do Coracao
    • Sao Paulo
      • São Paulo, Sao Paulo, Brazil
        • UNIFESP

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:

  • Male and females with 18 years and older
  • Confirmed diagnosis of SARS-CoV 2 infection
  • More than 3 days of symptoms related to COVID-19
  • Computed tomography (or Chest X-Ray) with COVID-19 alterations

  • Both of the criteria

    1. Need for oxygen supplementation to keep SPO2 > 93% OR need for mechanical ventilation for less than 24 hours before the randomization

    2. At least two of the following inflammatory tests above the cutoff :

      1. D-dimer > 1,000 ng/mL
      2. Reactive C protein > 5 mg/dL
      3. Ferritin > 300 mg/dL
      4. Lactate dehydrogenase > upper level limit

Exclusion Criteria:

  • Need for mechanical ventilation for 24 hours or more before the randomization
  • Hypersensitivity to tocilizumab
  • Patients without therapeutic perspective or in palliative care
  • Active non controlled infections
  • Other clinical conditions that contraindicate tocilizumab, according to the assistant physician
  • Low neutrophils count (< 0.5 x 109/L)
  • Low platelets count (< 50 x 109/L)
  • Liver disease, cirrhosis or elevated AST or ALT above 5 times the upper level limit
  • Renal disease with estimate glomerular filtration below 30 mL/min/1.72 m2 (MDRD or CKD-EPI scores)
  • Active diverticulitis
  • Breastfeeding women
  • Pregnancy

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

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
Single-dose tocilizumab of 8 mg/kg (maximum dose of 800mg). Best supportive care.
Drug: Tocilizumab
Single-dose infusion of 8 mg/kg. Maximum dose of 800 mg.
Other Names:
  • Actemra
No Intervention: Control arm
Best supportive care.

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
Evaluation of clinical status
Time Frame: Day 15 of the trial
Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)
Day 15 of the trial

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
All-cause mortality
Time Frame: 29 days after the randomization
All-cause mortality from randomization to day 28
29 days after the randomization
Hospital Mortality
Time Frame: 29 days after the randomization
Deaths that occur during hospital admission.
29 days after the randomization
Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale
Time Frame: 29 days after the randomization (evaluations at D8 and D15)
Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization
29 days after the randomization (evaluations at D8 and D15)
Evaluation of clinical status
Time Frame: 29 days after the randomization (evaluations at D8 and D29)
Evaluation of clinical status of patients on the day 8, 22 and 29 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)
29 days after the randomization (evaluations at D8 and D29)
Ventilator free days
Time Frame: 29 days after the randomization
Days alive and free from mechanical ventilation since randomization
29 days after the randomization
Time until oxygen support independence
Time Frame: 29 days after the randomization
Days from randomization to independence of oxygen support
29 days after the randomization
Need of mechanical ventilation support
Time Frame: 29 days after the randomization
Number of patients that were not at mechanical ventilation at randomization and that required that support.
29 days after the randomization
Days to mechanical ventilation support.
Time Frame: 29 days after the randomization

Number of days to mechanical ventilation for patients that were not receiving it at randomization.

For patients that were not in mechanical ventilation at randomization: number of days until that support was required.
29 days after the randomization
Duration of hospitalization
Time Frame: 29 days after the randomization
Lenght of hospitalization stay in survivors (in days)
29 days after the randomization
Other infections
Time Frame: 29 days after the randomization
Incidence of other infections (aside from SARS-CoV 2)
29 days after the randomization
Incidence of thromboembolic events
Time Frame: 29 days after the randomization
Incidence of thromboembolic events in patients with COVID-19
29 days after the randomization
Incidence of adverse events
Time Frame: 29 days after the randomization (specific evaluations at D8, D15 and D29)
Evaluation of adverse events, as well as serious and unexpected adverse events
29 days after the randomization (specific evaluations at D8, D15 and D29)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation of inflammatory tests and cytokines with clinical outcomes
Time Frame: 29 days after the randomization
Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality
29 days after the randomization
Exploratory evaluation of laboratory exams during hospitalization
Time Frame: 29 days after the randomization
Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams
29 days after the randomization
Evaluation of viral clearance of SARS-CoV2
Time Frame: Day 8 and 15 after randomization
Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab
Day 8 and 15 after randomization

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.
Beneficência Portuguesa de São Paulo

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.
Federal University of São Paulo
Hospital Israelita Albert Einstein
Hospital Moinhos de Vento
Brazilian Clinical Research Institute
Hospital do Coracao
Hospital Sirio-Libanes
Hospital Alemão Oswaldo Cruz
Brazilian Research In Intensive Care Network

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: Viviane C Veiga, MD, Beneficencia Portuguesa de Sao Paulo

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 8, 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.
July 8, 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.
July 21, 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).
May 24, 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.
May 24, 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.
May 27, 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.
August 26, 2020

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.
August 22, 2020

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.
August 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.
  • TOCIBRAS

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

product manufactured in and exported from the U.S.

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.

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