Phase II trial of combination therapy with favipiravir and corticosteroids for COVID-19

JRCT ID: jRCTs041200025

Registered date:01/07/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Coronavirus disease 2019 (COVID-19)
• Date of first enrollment: 01/07/2020
• Target sample size: 69
• Study type: Interventional
• Intervention(s): Combination therapy with favipiravir and methylprednisolone

Outcome(s)

• Primary Outcome: Proportion of patients who need mechanical ventilation or those who meet the criteria of tracheal intubation* within 14 days of initiation of treatment (*at least one of the following: 5 L/min or more of oxygen flux; unstable circulatory dynamics; or consciousness disturbance)

Secondary Outcome

- Proportion of patients who need tracheal intubation or death within 14 and 30 days of initiation of treatment
- Time to performing mechanical ventilation (including noninvasive positive pressure ventilation [NPPV]) or meeting the criteria of tracheal intubation
- Time to tracheal intubation or death
- 30-day mortality
- In-hospital mortality
- Time course of oxygenation (PaO2/FiO2)
- Viral load of SARS-CoV-2
- Time to becoming negative for PCR testing of SARS-CoV-2
- Proportion of positivity of antibody testing for SARS-CoV-2
- Adverse events

(Exploratory)
- Length of hospital stay
- Tracheal intubation
- Death
- Clinical recovery at 7 and 14 days after initiation of treatment

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients who developed pneumonia* and need inpatient treatment (*pneumonia is defined as the presence of a new infiltrate on a chest radiograph or a computed tomography scan in addition to at least one of the following: new or increased cough or sputum production, new pleuritic chest pain, new or increased dyspnea, fever (temperature >= 37.5 degrees) or hypothermia (temperature <35.0 degrees), leukocytosis [white blood cell count (WBC) >=10,000/mm3] or leukopenia (WBC <4,000/mm3), elevated level of CRP value (exceed the upper threshold of each study institution), or new hypoxemia or deterioration of hypoxemia)
2. Positive PCR or antigen testing of SARS-CoV-2
3. Within 12 days of onset of symptoms
4. Patients with hypoxemia who need oxygen therapy (who meet one of the following: SpO2 =< 93% on room air; arterial oxygen partial pressure (PaO2) =< 60 mmHg or PaO2/ fraction of inspired oxygen (FiO2) < 300; or AaDO2 >= 40)
5. Age >= 20 years old
6. Informed consent must be obtained prior to participation in this study
7. Patients who were registered in observational registry studies organized by National Center for Global Health and Medicine or Fujita Health University (This criterion will not be applicable after the approval of favipiravir)

Exclude criteria

1. Patients who meet the criteria of tracheal intubation (at least one of the following: 5 L/min or more of oxygen flux; unstable circulatory dynamics; or consciousness disturbance)
2. Intubated or tracheostomy was performed at time of initiation of treatment
3. Patients who need vasopressor(s) at time of initiation of treatment
4. Patients who are receiving systemic corticosteroids or immunosuppressive agents including biological ones at time of initiation of treatment
5. Patients with HIV or immunodeficiency disorders
6. Respiratory failure due to cardiac pulmonary edema
7. Apparent asthma attack
8. Apparent pulmonary embolism
9. Chronic pulmonary diseases (e.g., interstitial pneumonia and severe COPD) which potentially affect assessment of the efficacy of study treatment
10. Long term oxygen therapy
11. Malignant diseases which potentially affect assessment of the efficacy of study treatment
12. Complicating pneumonia due to apparent bacterial infection or aspiration
13. Patients who are receiving anti-SARS-CoV-2 agents (e.g., favipiravir, lopinavir/ritonavir, remdesivir, ciclesonide, etc.)
14. Patients who need to receive medications that affect the effect of corticosteroids (e.g., rifampicin, phenobarbital, phenytoin, and ephedrine)
15. Contraindication for use of favipiravir or corticosteroids (e.g., allergy to them)
16. Pregnant women and women suspected of being pregnant
17. Women who are not able to give informed consent regarding protected sexual intercourse from the initiation of favipiravir to 90 days after the end of its administration
18. Men or their partners who are not able to give informed consent regarding protected sexual intercourse from the initiation of favipiravir to 90 days after the end of its administration
19. Patients who may have difficulty receiving efficacy assessment due to dementia or mental disorders
20. Patients who are participating in other clinical studies which do not allow use of corticosteroids or those who are expected to participate in them
21. Patients in whom physicians in charge judged inappropriate for registration

Related Information

• Primary Sponsor: Yuichiro Shindo