Tocilizumab Versus Baricitinib in Patients With Severe COVID-19

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to investigate whether baricitinib is non-inferior to tocilizumab in severe COVID-19.

Detailed Description
-----------------
Patients with COVID-19 will be assigned to one of the two arms on 1:1 ratio based on the time point that PaO2/FiO2<200 will be observed. Patients aged 18 years or older with PaO2/FiO2 <200 at any time during their hospitalization will be included in the analysis irrespective of values in inflammatory markers, such as CRP and ferritin. Exclusion criteria will be: age<18 years, pregnancy, glomerular filtration rate<30 and application of mechanical ventilation prior patients' transfer to our Hospital. Each patient or the patient's legally authorized representative provided written or witnessed oral informed consent. Day 1 will be considered the first day that PaO2/FiO2<200 will be identified. Treatment with either tocilizumab or baricitinib will start from day 1. Primary and secondary outcomes will be assessed in the days described below. This study aims to investigate whether baricitinib is non-inferior to tocilizumab in patients with severe COVID-19. Two hundred fifty one (n=251) patients will be enrolled based on the following assumptions: 1) HR θ 1, 2) HR θο 1.5, 3) overall probability of event (primary end point) 0.6 (based on previous records of our hospital), 4) power 80%, 5) type I error α 5%.

Official Title
-----------------
Tocilizumab Versus Baricitinib in Hospitalized Patients With Severe COVID-19: an Open-label, Randomized Controlled Trial

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: Tocilizumab
* Drug: Baricitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - COVID-19, PaO2/FiO2<200 Exclusion Criteria: - Age<18 years, Pregnancy, Glomerular filtration rate<30, Application of mechanical ventilation prior patients' transfer to our Hospital

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Non-inferiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tocilizumab<br>tocilizumab plus usual care | Drug: Tocilizumab<br>* tocilizumab 8mg/kg single infusion (a second infusion within 48 hours can be applied upon clinician's discretion)<br>|
| Experimental: baricitinib<br>baricitinib plus usual care | Drug: Baricitinib<br>* The baricitinib intervention consists of baricitinib at a dose of 4 mg/day (given daily for up to 14 days or until discharge from hospital, whichever occurred first); however, 2 mg/day will be given if the patient has a baseline eGFR of 30 to less than 60 mL/min/1·73 m2<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical ventilation or death by day 28 |  | day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to discharge over the 28-day period |  | day 28 | 
| World Health Organization scale at day 10 [range from 0 (not infected) to 10 (dead)] |  | day 10 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Respiratory Distress Syndrome, COVID-19, PaO2/FiO2, Tocilizumab, Baricitinib