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

NCT04403685 | Terminated Phase 3 DMC

• 1 other identifier: TOCIBRAS
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 7

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.

Conditions

COVID; SARS Pneumonia; Cytokine Release Syndrome

Keywords

SARS-CoV 2; SARS Pneumonia; Tocilizumab; Cytokine release syndrom; Interleukin-6; Hyperinflammation

Outcome Measures

Primary Outcomes (1)

• Evaluation of clinical status

  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 Outcomes (12)

• All-cause mortality

  29 days after the randomization

• Hospital Mortality

  29 days after the randomization

• Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale

  29 days after the randomization (evaluations at D8 and D15)

• Evaluation of clinical status

  29 days after the randomization (evaluations at D8 and D29)

• Ventilator free days

  29 days after the randomization

Other Outcomes (3)

• Correlation of inflammatory tests and cytokines with clinical outcomes

  29 days after the randomization

• Exploratory evaluation of laboratory exams during hospitalization

  29 days after the randomization

• Evaluation of viral clearance of SARS-CoV2

  Day 8 and 15 after randomization

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Single-dose tocilizumab of 8 mg/kg (maximum dose of 800mg). Best supportive care.

Drug: Tocilizumab

Control arm

NO INTERVENTION

Best supportive care.

Interventions

Tocilizumab DRUG

Single-dose infusion of 8 mg/kg. Maximum dose of 800 mg.

Also known as: Actemra

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Need for oxygen supplementation to keep SPO2 \> 93% OR need for mechanical ventilation for less than 24 hours before the randomization
• At least two of the following inflammatory tests above the cutoff :
• D-dimer \> 1,000 ng/mL
• Reactive C protein \> 5 mg/dL
• Ferritin \> 300 mg/dL
• Lactate dehydrogenase \> upper level limit

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (7)

HCOR -Hospital do Coracao

São Paulo, São Paulo, 04004030, Brazil

Location

UNIFESP

São Paulo, São Paulo, Brazil

Location

HAOC - Hospital Alemao Oswaldo Cruz

São Paulo, 01323001, Brazil

Location

Beneficência Portuguesa de Sao Paulo

São Paulo, 01323900, Brazil

Location

HAOC - Hospital Alemao Oswaldo Cruz - unidade Vergueiro

São Paulo, Brazil

Location

HIAE - Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

HSL - Hospital Sírio Libanês

São Paulo, Brazil

Location

Related Publications (1)

• Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, Machado FR, Lopes RD, Berwanger O, Azevedo LCP, Avezum A, Lisboa TC, Rojas SSO, Coelho JC, Leite RT, Carvalho JC, Andrade LEC, Sandes AF, Pintao MCT, Castro CG Jr, Santos SV, de Almeida TML, Costa AN, Gebara OCE, de Freitas FGR, Pacheco ES, Machado DJB, Martin J, Conceicao FG, Siqueira SRR, Damiani LP, Ishihara LM, Schneider D, de Souza D, Cavalcanti AB, Scheinberg P; Coalition covid-19 Brazil VI Investigators. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021 Jan 20;372:n84. doi: 10.1136/bmj.n84.

  PMID: 33472855 DERIVED

MeSH Terms

Conditions

Cytokine Release Syndrome

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Viviane C Veiga, MD

  Beneficência Portuguesa de Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of research team

Model Details: Prospective, randomized, superiority, open-label, controlled trial. Randomization 1:1 to best supportive care (BSC) versus Tocilizumab + BSC

Study Record Dates

• First Submitted: May 24, 2020
• First Posted: May 27, 2020
• Study Start: May 8, 2020
• Primary Completion: July 8, 2020
• Study Completion: July 21, 2020
• Last Updated: August 26, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (7)