COVID-19 infection MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
University College Dublin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Confirmed SARS-CoV2 infection (as defined by positive PCR) • Evidence of hyper inflammatory state as evidenced by at least three of the following: o Documented temperature >38°C in the past 48 hours o IL6 >40 pg/ml, or in its absence D-dimer >1.5 µgFEU /ml. o Elevated CRP (>100mg/L) and/or a three-fold increase since presentation o Elevated ferritin X5 ULN o Elevated LDH (above the ULN) o Elevated fibrinogen (above the ULN) • Pulmonary infiltrates on chest imaging • Moderate to severe respiratory failure as defined by PaO2/FiO2=300mmHg • Aged 18 years or older Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: • Primary or secondary immunodeficiency • Use of significant immunosuppressive therapy in the last 3 months (not including hydroxychloroquine or short course of corticosteroids (defined as <400mg cumulative dose) • Active malignancy requiring treatment • Known active current or history of recurrent bacterial, mycobacterial, fungal or viral infections including history of untreated latent TB • History of diverticulitis or chronic ulcerative GI disease that might predispose to GI perforation • Severe allergic reaction to monoclonal antibodies • Pregnancy or breast feeding • AST / ALT with values greater than 10 times normal levels or history of significant liver disease that in the opinion of the investigator precludes use of an investigational agent • Neutrophils < 0.5 x109/L • Platelets < 50x109/L • Documented, uncontrolled sepsis caused by pathogen(s) other than COVID-19 • Presence of co-morbidities (including cognitive impairment and/or frailty) that, in the opinion of the investigator, should preclude use of an investigational agent • Current skin or soft tissue infection not controlled by antibiotics • Body weight = 30kg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and efficacy of standard dose versus low dose tocilizumab in adults with severe, non-critical, PCR-confirmed COVID-19 infection with evidence of progressive decline in respiratory function and evolving systemic inflammation on time to intubation, non-invasive ventilation and/or all-cause mortality.;Secondary Objective: In adults with severe, non-critical, PCR-confirmed COVID-19 infection with evidence of progressive decline in respiratory function and evolving systemic inflammation, to determine if single dose administration of tocilizumab will: - be safe, as defined by no difference in all-cause mortality compared to standard of care. - result in a longer time to intubation and non-invasive ventilation and lower all-cause mortality than standard of care. - result in similar time to intubation and noninvasive ventilation and all-cause mortality than standard of care.;Primary end point(s): Proportion of subjects at day 8 who have reached a composite primary endpoint of progression to intubation and ventilation, non-invasive ventilation or death;Timepoint(s) of evaluation of this end point: Day 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Prevalence of new SAE at day 8 2. Proportion of subjects at day 14 and 28 who have reached a composite primary endpoint of progression to intubation and ventilation, non-invasive ventilation or death 3. Day 14 and 28 survival 4. Incidence of intercurrent bacterial sepsis (positive blood culture) or septic shock (regardless of causative agent) 5. Change from baseline to day 8, 14 and 28 in markers of inflammation (CRP, ferritin, D-dimer, LDH and IL6) 6. Time to PCR negativity and change from baseline in quantitative SARS-CoV-2 viral load (measured by CT values) 7. Time to PCR negativity from date of onset of symptoms ;Timepoint(s) of evaluation of this end point: 1. Day 8 2. Day 14 and Day 28 3. Day 14 and Day 28 4. Time of event 5. Day 8, Day 14 and Day 28 6. Time of event 7. Time of event | — |
Countries
Ireland
Contacts
Public ContactQRAM
University College Dublin
Outcome results
None listed