Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of favipiravir combined with tocilizumab in the treatment of corona virus disease 2019.

Detailed Description
-----------------
In clinical institutions that enroll patients with corona virus disease 2019, three arms, multi-center, randomized and controlled methods are adopted. Patients are divided into three groups, favipiravir combined with tocilizumab group, favipiravir group and tocilizumab group. 150 patients are expected to be enrolled and the cases are allocated according to the ratio of 3( favipiravir combined with tocilizumab group): 1(favipiravir group): 1(tocilizumab group).

Official Title
-----------------
Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019-A Multicenter, Randomized and Controlled Clinical Trial Study

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

Intervention / Treatment
-----------------
* Drug: Favipiravir Combined With Tocilizumab
* Drug: Favipiravir
* Drug: Tocilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically diagnosed with Corona Virus Disease 2019 Increased interleukin-6 Sign the informed consent Subjects who can take medicine orally Agree to collect clinical samples Female subjects of childbearing age are not pregnant and agree to take effective contraception within 7 days of the last oral medication to ensure that they are not pregnant within 3-6 months Male patients agree to effective contraception within 7 days of last oral medication. Exclusion Criteria: Cases of severe vomiting that make it difficult to take the drug orally Allergic to Favipiravir or tocilizumab Pregnant and lactating women Subjects received specific antiviral drugs such as lopinavir / ritonavir, ribavirin, arbidol, chloroquine phosphate, hydroxychloroquine, and monoclonal antibodies within one week before admission. Cases of respiratory failure and requiring mechanical ventilation Cases of shock Combined organ failure requires ICU monitoring and treatment Predicted clinically that there is no hope of survival, or cases of deep coma that do not respond to supportive treatment measures within three hours of admission Alanine aminotransferase / Aspartate aminotransferase> 5 times of upper limit of normal Neutrophils <0.5 × 10^9 / L, platelets less than 50 × 10^9 / L Clear diagnosis of rheumatoid immunity, malignant tumors and other related diseases Long-term oral anti-rejection drugs or immunomodulatory drugs Allergic reactions to tocilizumab or any excipients Patients with active hepatitis, tuberculosis, and definite bacterial and fungal infections Organ transplant patients Patients with mental disorders

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favipiravir Combined With Tocilizumab group<br>Favipiravir: On the 1st day, 1600mg each time, twice a day; from the 2nd to the 7th day, 600mg each time, twice a day. Oral administration, the maximum number of days taken is not more than 7 days. Tocilizumab:The first dose is 4   8mg/kg and the recommended dose is 400mg. For fever patients, an additional application (the same dose as before) is given if there is still fever within 24 hours after the first dose and the interval between two medications ≥ 12 hours.Intravenous infusion, The maximum of cumulative number is two, and the maximum single dose does not exceed 800mg. | Drug: Favipiravir Combined With Tocilizumab<br>* Favipiravir: On the 1st day, 1600mg each time, twice a day; from the 2nd to the 7th day, 600mg each time, twice a day. Oral administration, the maximum number of days taken is not more than 7 days. Tocilizumab:The first dose is 4   8mg/kg and the recommended dose is 400mg. For fever patients, an additional application (the same dose as before) is given if there is still fever within 24 hours after the first dose and the interval between two medications ≥ 12 hours.Intravenous infusion, The maximum of cumulative number is two, and the maximum single dose does not exceed 800mg.<br>|
| Active Comparator: Favipiravir group<br>On the 1st day, 1600mg each time, twice a day; from the 2nd to the 7th day, 600mg each time, twice a day. Oral administration, the maximum number of days taken is not more than 7 days. | Drug: Favipiravir<br>* On the 1st day, 1600mg each time, twice a day; from the 2nd to the 7th day, 600mg each time, twice a day. Oral administration, the maximum number of days taken is not more than 7 days.<br>|
| Active Comparator: Tocilizumab group<br>The first dose is 4   8mg/kg and the recommended dose is 400mg. For fever patients, an additional application (the same dose as before) is given if there is still fever within 24 hours after the first dose and the interval between two medications ≥ 12 hours.Intravenous infusion, The maximum of cumulative number is two, and the maximum single dose does not exceed 800mg. | Drug: Tocilizumab<br>* The first dose is 4   8mg/kg and the recommended dose is 400mg. For fever patients, an additional application (the same dose as before) is given if there is still fever within 24 hours after the first dose and the interval between two medications ≥ 12 hours.Intravenous infusion, The maximum of cumulative number is two, and the maximum single dose does not exceed 800mg.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical cure rate | Definition of clinical cure: The viral load of the respiratory specimen was negative for two consecutive times (the interval between the two tests was greater than or equal to one day), the lung image improved, and the body temperature returned to normal for more than 3 days, and the clinical manifestation improved. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral nucleic acid test negative conversion rate and days from positive to negative |  | 14 days after taking medicine | 
| Duration of fever |  | 14 days after taking medicine | 
| Lung imaging improvement time |  | 14 days after taking medicine | 
| Mortality rate because of Corona Virus Disease 2019 |  | 3 months | 
| Rate of non-invasive or invasive mechanical ventilation when respiratory failure occurs |  | 3 months | 
| Mean in-hospital time |  | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Novel coronavirus pneumonia, Favipiravir, Tocilizumab