Official Title
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)
Brief Summary

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.

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.

Terminated
COVID
SARS Pneumonia
Cytokine Release Syndrome

Drug: Tocilizumab

Single-dose infusion of 8 mg/kg. Maximum dose of 800 mg.
Other Name: Actemra

Eligibility Criteria

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

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Brazil
Locations

UNIFESP
São Paulo, Sao Paulo, Brazil

HCOR -Hospital do Coracao
Sao Paulo, SP, Brazil

HAOC - Hospital Alemao Oswaldo Cruz
Sao Paulo, Brazil

Beneficência 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
Sao Paulo, Brazil

Viviane C Veiga, MD, Principal Investigator
Beneficência Portuguesa de Sao Paulo

Beneficência Portuguesa de São Paulo
NCT Number
Keywords
SARS-CoV 2
SARS Pneumonia
Tocilizumab
Cytokine release syndrom
Interleukin-6
Hyperinflammation
MeSH Terms
Pneumonia
Cytokine Release Syndrome