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

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Favipiravir Combined With Tocilizumab; Drug: Favipiravir; Drug: Tocilizumab

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).

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
      • Contact: Haichao Li; Phone Number: 18511129044
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Guiqiang Wang
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Ezhou Central Hospital
      • Contact: Yuhong Qin; Phone Number: 13810634388
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Huoshenshan Hospital of Wuhan
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Jinyintan Hospital of Wuhan
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Wuhan Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinically diagnosed with Corona Virus Disease 2019
2. Increased interleukin-6
3. Sign the informed consent
4. Subjects who can take medicine orally
5. Agree to collect clinical samples
6. 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
7. Male patients agree to effective contraception within 7 days of last oral medication.

Exclusion Criteria:

1. Cases of severe vomiting that make it difficult to take the drug orally
2. Allergic to Favipiravir or tocilizumab
3. Pregnant and lactating women
4. Subjects received specific antiviral drugs such as lopinavir / ritonavir, ribavirin, arbidol, chloroquine phosphate, hydroxychloroquine, and monoclonal antibodies within one week before admission.
5. Cases of respiratory failure and requiring mechanical ventilation
6. Cases of shock
7. Combined organ failure requires ICU monitoring and treatment
8. 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
9. Alanine aminotransferase / Aspartate aminotransferase> 5 times of upper limit of normal
10. Neutrophils <0.5 × 10^9 / L, platelets less than 50 × 10^9 / L
11. Clear diagnosis of rheumatoid immunity, malignant tumors and other related diseases
12. Long-term oral anti-rejection drugs or immunomodulatory drugs
13. Allergic reactions to tocilizumab or any excipients
14. Patients with active hepatitis, tuberculosis, and definite bacterial and fungal infections
15. Organ transplant patients
16. Patients with mental disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Favipiravir Combined With Tocilizumab group; 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; 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.
ACTIVE_COMPARATOR: Favipiravir group; 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; 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.
ACTIVE_COMPARATOR: Tocilizumab group; 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; 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.

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	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

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 8, 2020
• Primary Completion (ANTICIPATED): May 1, 2020
• Study Completion (ANTICIPATED): May 1, 2020

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 14, 2020
• First Posted (ACTUAL): March 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2020
• Last Update Submitted That Met QC Criteria: April 8, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Tocilizumab; Favipiravir; Novel coronavirus pneumonia
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Virus Diseases; Anti-Infective Agents; Antiviral Agents; Favipiravir
• Other Study ID Numbers: 2020YFC0844100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No