A RCT – Safety & Efficacy of Tocilizumab – Tx of Severe COVID-19: ARCHITECTS

Overview

The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.

Full Title of Study: “A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19″

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: December 31, 2021

Interventions

  • Drug: Tocilizumab
    • Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen.
  • Drug: Placebo
    • Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.

Arms, Groups and Cohorts

  • Experimental: Tocilizumab (TCZ) Arm
    • Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen.
  • Placebo Comparator: Placebo Arm
    • Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.

Clinical Trial Outcome Measures

Primary Measures

  • Clinical status (on a 7-point ordinal scale) at day 28
    • Time Frame: up to day 28
    • Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death

Secondary Measures

  • Clinical improvement
    • Time Frame: up to day 28
    • ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
  • Mechanical Ventilation
    • Time Frame: up to day 28
    • iv. Incidence of mechanical ventilation v. Ventilator-free days
  • Oxygenation
    • Time Frame: up to day 28
    • vi. Duration of time on supplemental oxygen

Participating in This Clinical Trial

Inclusion Criteria

  • ii. Hospitalized with COVID-19 pneumonia, based on chest X-ray or CT scan AND iii. Evidence of hyperinflammation: IL-6>40pg/mL (if available) OR CRP >2 mg/dL OR ferritin >2000 ng/mL AND iv. One or more of the following: impending need for requiring invasive or non-invasive mechanical ventilation OR shock requiring vasopressor (without evidence of bacterial / fungal infection) OR need for extracorporeal membrane oxygenation (ECMO) OR severe, refractor ARDS (PaO2/FiO2<200 mmHg)

Exclusion Criteria

Known severe allergic reactions to tocilizumab or other monoclonal antibodies

  • Active tuberculosis infection based on history
  • Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
  • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
  • Have received oral anti-rejection or immunomodulatory drugs (including tocilizumab) with the past 6 months
  • Participating in other drug clinical trials (participation in COVID-19 trials allowed)
  • Self-reported pregnant or breastfeeding
  • Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 10 x upper limit of normal (ULN) detected within 24 hours at baseline
  • Absolute neutrophil count (ANC) < 1000/mL at baseline
  • Platelet count < 50,000/mL at baseline

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 95 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Queen’s Medical Centre
  • Provider of Information About this Clinical Study
    • Principal Investigator: Todd Seto, Director Academic Liaison and Research – Queen’s Medical Centre
  • Overall Official(s)
    • Todd Seto, MD, Principal Investigator, The Queen’s Medical Center
  • Overall Contact(s)
    • Todd Seto, MD, 808 354-3533, tseto@queens.org

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