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

Sponsor
Beneficência Portuguesa de São Paulo (Other)
Overall Status
Terminated
CT.gov ID
NCT04403685
Collaborator
Hospital do Coracao (Other), Hospital Israelita Albert Einstein (Other), Hospital Sirio-Libanes (Other), Hospital Alemão Oswaldo Cruz (Other), Brazilian Research In Intensive Care Network (Other), Hospital Moinhos de Vento (Other), Brazilian Clinical Research Institute (Other), Federal University of São Paulo (Other)
129
Enrollment
7
Locations
2
Arms
2.4
Actual Duration (Months)
18.4
Patients Per Site
7.6
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
129 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Prospective, randomized, superiority, open-label, controlled trial. Randomization 1:1 to best supportive care (BSC) versus Tocilizumab + BSCProspective, randomized, superiority, open-label, controlled trial. Randomization 1:1 to best supportive care (BSC) versus Tocilizumab + BSC
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
May 8, 2020
Actual Primary Completion Date :
Jul 8, 2020
Actual Study Completion Date :
Jul 21, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tocilizumab

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

Drug: Tocilizumab
Single-dose infusion of 8 mg/kg. Maximum dose of 800 mg.
Other Names:
  • Actemra

    		•
    No Intervention: Control arm

    Best supportive care.

    Outcome Measures

    Primary Outcome Measures

    1. Evaluation of clinical status [Day 15 of the trial]

      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)

    Secondary Outcome Measures

    1. All-cause mortality [29 days after the randomization]

      All-cause mortality from randomization to day 28

    2. Hospital Mortality [29 days after the randomization]

      Deaths that occur during hospital admission.

    3. Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale [29 days after the randomization (evaluations at D8 and D15)]

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

    4. Evaluation of clinical status [29 days after the randomization (evaluations at D8 and D29)]

      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)

    5. Ventilator free days [29 days after the randomization]

      Days alive and free from mechanical ventilation since randomization

    6. Time until oxygen support independence [29 days after the randomization]

      Days from randomization to independence of oxygen support

    7. Need of mechanical ventilation support [29 days after the randomization]

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

    8. Days to mechanical ventilation support. [29 days after the randomization]

      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.

    9. Duration of hospitalization [29 days after the randomization]

      Lenght of hospitalization stay in survivors (in days)

    10. Other infections [29 days after the randomization]

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

    11. Incidence of thromboembolic events [29 days after the randomization]

      Incidence of thromboembolic events in patients with COVID-19

    12. Incidence of adverse events [29 days after the randomization (specific evaluations at D8, D15 and D29)]

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

    Other Outcome Measures

    1. Correlation of inflammatory tests and cytokines with clinical outcomes [29 days after the randomization]

      Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality

    2. Exploratory evaluation of laboratory exams during hospitalization [29 days after the randomization]

      Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams

    3. Evaluation of viral clearance of SARS-CoV2 [Day 8 and 15 after randomization]

      Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 :

    3. D-dimer > 1,000 ng/mL

    4. Reactive C protein > 5 mg/dL

    5. Ferritin > 300 mg/dL

    6. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UNIFESP São Paulo Sao Paulo Brazil
    2 HCOR -Hospital do Coracao Sao Paulo SP Brazil 04004030
    3 HAOC - Hospital Alemao Oswaldo Cruz Sao Paulo Brazil 01323001
    4 Beneficência Portuguesa de Sao Paulo Sao Paulo Brazil 01323900
    5 HAOC - Hospital Alemao Oswaldo Cruz - unidade Vergueiro Sao Paulo Brazil
    6 HIAE - Hospital Israelita Albert Einstein Sao Paulo Brazil
    7 HSL - Hospital Sírio Libanês Sao Paulo Brazil

    Sponsors and Collaborators

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

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Dr Rozana Mesquita Ciconelli, Head of research team, Beneficência Portuguesa de São Paulo
    ClinicalTrials.gov Identifier:
    NCT04403685
    Other Study ID Numbers:
    • TOCIBRAS
    First Posted:
    May 27, 2020
    Last Update Posted:
    Aug 26, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Dr Rozana Mesquita Ciconelli, Head of research team, Beneficência Portuguesa de São Paulo
    SARS-CoV 2
    SARS Pneumonia
    Tocilizumab
    Cytokine release syndrom
    Interleukin-6
    Hyperinflammation
    Additional relevant MeSH terms:
    Pneumonia
    Cytokine Release Syndrome

    Study Results

    No Results Posted as of Aug 26, 2020