Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19

Study Overview
=================
Brief Summary
-----------------
The cytokine storms mediated by over production of proinflammatory cytokines have been observed in a large population of critically ill patients infected with COVID-19. Patients diagnosed with cytokine storms progress to cardiovascular collapse, multiple organ dysfunction and death rapidly. Therefore, early identification, treatment and prevention of the cytokine storms are of crucial importance for the patients. Immuomedulator such as interleukin-6 (IL-6) antagonist, emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In this study, we aimed to evaluate the safety and efficacy of anti-IL6 alone vs anti-IL6 corticosteroid combination in patients with COVID-19 pneumonia

Detailed Description
-----------------
This study will provide further insight whether anti-IL6 alone provide same efficacy and clinical outcome with reasonable side effects profile compared to anti-IL6 + corticosteroid and might serve as a corticosteroid sparing agents in COVID-19 patient with cytokine storms. Data elements will be retrieved from VIRUS registry which is a prospective, non-interventional, multi-center, multi-national observational cross sectional study

Official Title
-----------------
Clinical Outcome of Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19 Cytokine Release Syndrome

Conditions
-----------------
Critical Illness, Corona Virus Infection, Cytokine Release Syndrome

Intervention / Treatment
-----------------
* Drug: Interleukin 6 (IL6) Antagonist
* Drug: Interleukin 6 (IL6) Antagonist and corticosteroids
* Drug: corticosteroid alone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult Critically ill patients COVID-19 PCR positive Presence of clinical and radiological signs of progressive disease, and laboratory evidence indicative of risk for cytokine storm complications. Received anti-IL6 or corticosteroids as part of COVID-19 treatment Exclusion Criteria: Non COVID-19 related admissions Repeated Admission to ICUs/Hospital Patient did not receive anti-IL6 or corticosteroids

Ages Eligible for Study
-----------------
Minimum Age: 14 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental<br>anti-IL-6 drugs (tocilizumab and siltuximab) | Drug: Interleukin 6 (IL6) Antagonist<br>* anti-IL6 alone<br>* Other names: Siltuximab;|
| Active Comparator 1<br>Anti-IL-6 drugs (tocilizumab and siltuximab) and corticosteroids combination | Drug: Interleukin 6 (IL6) Antagonist and corticosteroids<br>* anti-IL6 + corticosteroid combination<br>|
| Active Comparator 2<br>corticosteroids alone | Drug: corticosteroid alone<br>* dexamethasone, hydrocortisone, methylprednisolone, prednisone. All steroids  other than dexamethasone will be converted to dexamethasone equivalent<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-Free Days | The median ventilator-free days will be calculated as calendar days with no ventilator support to day 28 . Participants who die before day 28 are assigned zero free days. | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median duration of ventilation | From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days whichever occurs first. | Up to Day 28 | 
| Median change in the PaO2/FiO2 | Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) | Up to Day 28 | 
| Vasopressor-Free days | The median vasopressor-free days will be calculated as calendar days with no vasopressor support to day 28. Participants who die before day 28 are assigned zero free days. | Up to Day 28 | 
| Duration of ICU Stay | To compare ICU LOS | Up to 28 days | 
| Duration of Hospital Stay | To compare hospital LOS | Up to 28 days | 
| Mortality Rate | Death that occurs during 28 days | Up to Day 28 | 
| Percentage of participants with adverse events [transaminitis, hyperglycemia] | adverse events that occurs during 28 days | Up to 28 days | 
| Concentration of Ferritin, IL6, D dimer, fibrinogen, C-reactive protein (CRP), Lactate dehydrogenase (LDH) and absolute lymphocyte count and their correlation with the effectiveness of the treatment | Concentration of inflammatory markers | Up to 28 days | 
| Rate of superinfection (bacterial, viral, invasive fungal infections) |  | Up to 28 days | 
| Time to the first COVID 19 test negative |  | Up to 28 days |