COVID-19: Salvage TOcilizumab as a Rescue Measure

Study Overview
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Brief Summary
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Evaluating the efficacy of Tocilizumab in hospitalized patients in the inflammatory phase of COVID-19. Randomization 2:1 (TCZ:standard of care).

Official Title
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COVID-19: Salvage TOcilizumab as a Rescue Measure. Use of Tocilizumab in the Inflammatory Phase of COVID-19 / New Coronavirus Disease

Conditions
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Covid19

Intervention / Treatment
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* Drug: iv Tocillizumab (TCZ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consaent obtained hospitalized with COVID-19 disease Age >/= 18 years SARS CoV-2 NhO posit Sp=2 </93% on ambient air or respiratory rate >30 /min Any 2 of the 4: P-IL-6 > 2 x ULN / P-ferritin > 2 x ULN / P-FIDD >1.5 mg/l / P- CRP >40 mg/l without obvious presence of bacterial infection (normal values: P -IL-6 <5.9 ng/l; P-ferritin, men 30-400 mikrog/l, women 13-150 mikrog/l ; P-FIDD (Fibrin degradation products, D-dimer) <0.5 mg/l; P-CRP <10 mg/l) Exclusion Criteria: Known severe allergic reactions to monoclonal antibodies Active confirmed tuberculosis with ongoing treatment or obvious tuberculosis or obvious other bacterial, fungal or viral infection (besides COVID-19) In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Long-term oral anti-rejection or immunomodulatory drugs (including corticosteroids equivalent to methylprednison 15mg/day) Pregnant or lactating women. If needed, exclusion of pregnancy should be performed by laboratory test (U-hCG-O). Participating in other drug clinical trials Absolute neutrophil count < 1 x10E9/l Platelet count <50 x10E9/l ALAT >10x ULN

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocilizumab (TCZ)<br>Participants will receive one infusion of iv TCZ (according to weight of patient) | Drug: iv Tocillizumab (TCZ)<br>* Participants are randomized (2:1) to receive TCZ or Standard of Care<br>|
| No Intervention: standard of care (no TCZ)<br>Participants will receive standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status at day 28 | (assessed using 7-category ordinal scale) 7 death 6 in ICU with ECMO/ mechanical ventilation 5 in ICU, no ECMO/ mechanical ventilation 4 in hospital, not ICU, needs supplementary oxygen 3 in hospital, not ICU, no supplementary oxygen 2 not in hospital, but not back to normal 1 not in hospital, back to normal | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement | defined as a National Early Warning Score 2 (NEWS2) of>/=2 maintained for 24 hours | 28 days | 
| Time to decline of at least 2 categories | relative on a 7-category ordinalscale of clinical status | 28 days | 
| Incidence of mechanical and/or non-invasive ventilation | (mode and duration of respiratory support) Hospital day when respiratory support needed with non-invasive ventilation - and duration. Hospital day when respiratory support needed by invasive mechanical ventilation -and duration. | 28 days | 
| Number of ventilator-free days to day 28 | days not in ventilator | 28 days | 
| Organ failure free days to day 28 | days without organ failure | 28 days | 
| Incidence of ICU stay | ICU admission day | 28 days | 
| Duration of ICU stay | days on ICU | 28 days | 
| Time to clinical failure | time to death, mechanical ventilation, or ICU admission (whichever occurs first) | 28 days | 
| SAPS II | during ICU stay SAPS II = simplified acute physiology score II min 0 (best), max 163 (worst) | 28 days | 
| CCI | during ICU stay CCI = Charlson Comorbidity Index min 0 (best), max 37 (worst) | 28 days | 
| APACHE II | during ICU stay APACHE II = acute physiology and chronic health evaluation II min 0 (best), max 71 (worst) | 28 days | 
| SOFA 6 | during ICU stay SOFA 6 = sequential organ failure assessment min 0 (best), max 24 (worst) | 28 days | 
| Mortality rate | during and end of period of 28 days | 28 days | 
| Time to hospital discharge or ready for discharge | as evidenced by normal body temperature and respiratory rate and stable oxygen saturation on ambient air or </=2 l supplemental oxygen | 28 days | 
| Duration of supplemental oxygen | days on suppl oxygen | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, new coronavirus disease, tocilizumab