Clinical trial NCT04377503: Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cytokine Release Syndrome
Covid-19
Keywords: Cytokine release syndrome
COVID-19
Tocilizumab
Methylprednisolone
Safety
Efficacy
Lead sponsor: Hospital Sao Domingos
Sponsor class: OTHER
First posted: 2020-05-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Prospective randomized controlled phase 2 study
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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

Primary outcomes:
measure: Patient clinical status 15 days after randomization
timeFrame: 15 days after randomization
Secondary outcomes:
measure: Improving oxygenation
timeFrame: 15 days
measure: Thorax CT improvement
timeFrame: 10 days
measure: ICU length of stay
timeFrame: 28 days
measure: Duration of mechanical ventilation
timeFrame: 28 days
measure: Incidence of acute kidney (AKI) with necessity of renal replacement therapy
timeFrame: 15 days
Other outcomes:
Locations:
city: Sao Luis
country: Brazil
facility: Hospital Sao Domingos
state: MA
Study officials:
affiliation: Hospital Sao Domingos
name: PEDRO B FROTA, MD
role: PRINCIPAL_INVESTIGATOR
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