Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19

March 14, 2022 updated by: José Raimundo Araujo de Azevedo, Hospital Sao Domingos

Comparison of the Efficacy and Safety of Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19. A Prospective Randomized Controlled Phase II Trial

This study compare the efficacy and safety of tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

In December 2019, several patients were diagnosed with pneumonia of undefined etiology in Wuhan, China. A few days later, a virus was identified as the etiologic agent. It was a new beta coronavirus that received the name of Severe Acute Respiratory Syndrome Coroinavirus (SARS-COV-2).

The disease quickly spread to the Wuhan region and in March reached northern Italy and soon across Europe. On March 14, the World Health Organization declared that COVID-19 had acquired seriousness and spread to be defined as a pandemic.

Since then, COVID-19 has challenged the ability of rich countries to meet the demand for beds, especially ICU beds, and it has also challenged science in search of effective treatment, while in record time research centers begins testing with a vaccine.

Although a significant percentage of patients with COVID-19 have a benign evolution, around 20% of cases the disease acquires sufficient severity from the point of view of lung involvement to justify treatment in the ICU. In addition, around 5% of patients evolve with extremely serious forms and are associated with a lethality of up to 60%. Some of these patients demonstrated in studies alterations in cellular and humoral immunity compatible with the cytokine release syndrome, an entity that has been described complicating the use of antineoplastic drugs and viral infections.

At this moment several studies, some of them with conclusions already seek to identify effective forms of treatment. Antiviral drugs such as Lopinavir-Ritonavir, which has already been tested in a prospective randomized study and has not been shown to be effective. The antiviral rendecivir was tested in a preliminary study brought a positive expectation and the hydroxychloroquine in studies with small samples is the drug that currently meets the highest expectations. None of these drugs, however, is effective in the case of the group of patients who acquire severity as a result of what has been called a cytokine storm. In this case, expectations are turned to interleukin antagonists and corticosteroids. Among the interleukin antagonists the drug that meets the most expectations is Tocilizumab, an interleukin-6 antagonist that has proven efficacy in the cytokine release syndrome caused by antineoplastic drugs. There are currently ongoing studies analyzing the role of tocilizumab and, at the same time, and along the same line, corticosteroids are being tested. There is currently no prospective randomized study examining the role of tocilizumab. Regarding corticosteroids, the only evidence comes from a retrospective study involving 201 patients with COVID pneumonia 19 and acute respiratory distress syndrome. This study showed an association between corticosteroids and reduced risk of death (HR 0.38; p = 0.003).

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • 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

  • Brazil
    • MA
      • Sao Luis, MA, Brazil, 65060-000
        • Hospital São Domingos

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

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Men and non-pregnant women over 18 years old COVID diagnosis confirmed by real time polymerase chain reaction (RT-PCR) Pao2 / FIO2 <200 Laboratory: high sensitivity C reactive protein> 5 mg / L; lactic dehydrogenase (LDH ) > 245 U / l; Ferritin> 300; D-dimer> 1500; Interleukin-6> 7.0 pg / ml.

Exclusion Criteria:

  • Known sensitivity/Allergy to tocilizumab
  • Active tuberculosis
  • Pregnancy
  • Individuals, in the opinion of the investigators where progression to death is imminent and inevitable in the next 24 hours

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: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tocilizumab
Patients will receive Tocilizumab, 8 mg / kg diluted in 100 ml of saline and administered IV for 60 minutes. The dose will be repeated only once 12 hours after the first dose.
Drug: Tocilizumab 180 MG/ML
Tocilizumab 8 mg/kg diluted in 100 ml of saline administered in 60 minutes. The dose will be repeated after 12 hours.
Drug: Methylprednisolone Sodium Succinate
Patients will receive methylprednisolone at a dose of 1.5 mg / kg / day divided into 2 daily doses for 7 days. Then they will receive 1 mg / kg / day for another 7 days. Finally 0.5 mg / kg / day until 21 days of use
Active Comparator: Methylprednisolone
Patients will receive methylprednisolone at a dose of 1.5 mg / kg / day divided into 2 daily doses for 7 days. Then they will receive 1 mg / kg / day for another 7 days in two daily doses. Finally 0.5 mg / kg / day for another 7 days.
Drug: Tocilizumab 180 MG/ML
Tocilizumab 8 mg/kg diluted in 100 ml of saline administered in 60 minutes. The dose will be repeated after 12 hours.
Drug: Methylprednisolone Sodium Succinate
Patients will receive methylprednisolone at a dose of 1.5 mg / kg / day divided into 2 daily doses for 7 days. Then they will receive 1 mg / kg / day for another 7 days. Finally 0.5 mg / kg / day until 21 days of use

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient clinical status 15 days after randomization
Time Frame: 15 days after randomization
A seven-category ordinal scale consisting of: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
15 days after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improving oxygenation
Time Frame: 15 days
Improvement in PaO2/FIO2
15 days
Thorax CT improvement
Time Frame: 10 days
Improvement in the computed tomography between D0 and D10 after randomization
10 days
ICU length of stay
Time Frame: 28 days
Duration o ICU stay in days
28 days
Duration of mechanical ventilation
Time Frame: 28 days
Days of mechanical ventilation
28 days
Incidence of acute kidney (AKI) with necessity of renal replacement therapy
Time Frame: 15 days
AKI according to Kidney Disease Improving Global Outcomes (KDIGO)
15 days

Collaborators and Investigators

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

Sponsor

Hospital Sao Domingos

Investigators

  • Principal Investigator: PEDRO B FROTA, MD, Hospital São Domingos

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)

May 1, 2020

Primary Completion (Actual)

August 31, 2020

Study Completion (Actual)

November 30, 2020

Study Registration Dates

First Submitted

May 2, 2020

First Submitted That Met QC Criteria

May 4, 2020

First Posted (Actual)

May 6, 2020

Study Record Updates

Last Update Posted (Actual)

March 29, 2022

Last Update Submitted That Met QC Criteria

March 14, 2022

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • covid-19 hsd

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.

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