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COVIDPhase 3TOCIBRASNCT04403685

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

A Phase 3 study testing Tocilizumab in people with COVID and SARS Pneumonia, run by Beneficência Portuguesa de São Paulo at 7 sites in Brazil.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID, SARS Pneumonia, Cytokine Release Syndrome
What is being tested?
Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
129 participants
Where
7 sitesBrazil
Study dates
8 May 2020to 21 Jul 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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)
Show all 12Show fewer
  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Brazil7 sites

  • HCOR -Hospital do Coracao

    São Paulo, São Paulo, 04004030

  • UNIFESP

    São Paulo, São Paulo

  • HAOC - Hospital Alemao Oswaldo Cruz

    São Paulo, 01323001

  • Beneficência Portuguesa de Sao Paulo

    São Paulo, 01323900

  • HAOC - Hospital Alemao Oswaldo Cruz - unidade Vergueiro

    São Paulo

  • HIAE - Hospital Israelita Albert Einstein

    São Paulo

  • HSL - Hospital Sírio Libanês

    São Paulo

Other trials in Brazil

About this study

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)

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.

Read the 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.

Being tested
Tocilizumab
Keywords
SARS-CoV 2, SARS Pneumonia, Tocilizumab, Cytokine release syndrom, Interleukin-6, Hyperinflammation
Medical subject headings
Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TocilizumabDrug

    Also called Actemra

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

Study groups in NCT04403685
Study groupRoleWhat they receive
TocilizumabExperimentalSingle-dose tocilizumab of 8 mg/kg (maximum dose of 800mg). Best supportive care.
Receives: Drug: Tocilizumab
Control armNo interventionBest supportive care.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Day 15 of the trial

Secondary outcomes (12)

  1. All-cause mortality

    All-cause mortality from randomization to day 28

    Measured: 29 days after the randomization

  2. Hospital Mortality

    Deaths that occur during hospital admission.

    Measured: 29 days after the randomization

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

    Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization

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

  4. Evaluation of clinical status

    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)

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

  5. Ventilator free days

    Days alive and free from mechanical ventilation since randomization

    Measured: 29 days after the randomization

  6. Time until oxygen support independence

    Days from randomization to independence of oxygen support

    Measured: 29 days after the randomization

  7. Need of mechanical ventilation support

    Number of patients that were not at mechanical ventilation at randomization and that required that support.

    Measured: 29 days after the randomization

  8. Days to mechanical ventilation support.

    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.

    Measured: 29 days after the randomization

  9. Duration of hospitalization

    Lenght of hospitalization stay in survivors (in days)

    Measured: 29 days after the randomization

  10. Other infections

    Incidence of other infections (aside from SARS-CoV 2)

    Measured: 29 days after the randomization

  11. Incidence of thromboembolic events

    Incidence of thromboembolic events in patients with COVID-19

    Measured: 29 days after the randomization

  12. Incidence of adverse events

    Evaluation of adverse events, as well as serious and unexpected adverse events

    Measured: 29 days after the randomization (specific evaluations at D8, D15 and D29)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2020
  2. Study start8 May 2020
  3. Primary completion8 Jul 2020
  4. Study completion21 Jul 2020

Why it stopped: Safety

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomized, superiority, open-label, controlled trial. Randomization 1:1 to best supportive care (BSC) versus Tocilizumab + BSC
Masking
None (open label)
Enrolment
129 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04403685
Sponsor's protocol ID
TOCIBRAS
Acronym
TOCIBRAS
Status last verified
Aug 2020
First submitted
24 May 2020
Last updated
26 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33472855

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tocilizumab in people with COVID and SARS Pneumonia, run by Beneficência Portuguesa de São Paulo at 7 sites in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Safety). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of clinical status (time frame: Day 15 of the trial). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04403685, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2020.

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