COVID-19
Conditions
Brief summary
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.
Interventions
DRUGTocilizumab
Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen.
DRUGPlacebo
Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.
Sponsors
Queen's Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical status (on a 7-point ordinal scale) at day 28 | up to day 28 | Clinical Status 7-point ordinal scale: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygenation | up to day 28 | vi. Duration of time on supplemental oxygen |
| Clinical improvement | 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 | up to day 28 | iv. Incidence of mechanical ventilation v. Ventilator-free days |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTodd Seto, MD
The Queen's Medical Center
Outcome results
None listed