• Pregnant (female of childbearing age with positive urine pregnancy test) or miscarriage or within 2 weeks after delivery
• Severe or critical clinical condition as per NMC clinical guideline for COVID19
• Chronic liver with ALT/AST increased 5 times higher than the upper limit of normal or with Child Pugh C
• Creatinine clearance (Cockcroft-Gault Equation) < 30 ml/min or having hemodialysis/peritoneal dialysis
• Known allergy or hypersensitivity to Favipiravir
• Gout or history of gout or hyperuricemia two times the upper limit of normal
• If using Remdesivir, Lopinavir-ritonavir, Hydroxychloroquine or any other antiviral drug with potential effect against SARS-CoV-2 virus
• Lactating female
• Asymptomatic COVID-19 cases
• Mild COVID-19 cases not meeting the inclusion criteria symptoms

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Severe COVID-19 disease: defined as presence of SpO2 less than 93% on room air or a PaO2 to FiO2 ratio of 300 or lower at time of enrolment
• Patients on ventilatory support
• Cardiac dysfunction that would preclude treatment with hydroxychloroquine
• Renal dysfunction (estimated glomerular filtration rate less than 30 ml/min)
• Hepatic dysfunction
• Gout or a history of gout
• Pregnant or breastfeeding women
• Patients with a known allergy to an intervention medication
• Patients with glucose-6-phosphatase deficiency
• Readmission due to Covid-19 disease
• Participants in any other COVID-19 disease trial
• Patients on immunosuppressants, HIV patients, cancer patients who received chemotherapy within the past 6 months, or who were on chronic oral steroids.

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• Hypersensitivity to favipiravir and/or other components of the study drug.
  Impossibility of CT procedure (for example, gypsum dressing or metal structures in the field of imaging).
  The need to use drugs from the list of prohibited therapy.
  Need for treatment in the intensive care unit.
  Impaired liver function (AST and/or ALT ≥ 2 UNL and/or total bilirubin ≥ 1.5 UNL) at the time of screening.
  Impaired kidney function (creatinine clearance according to Cockcroft-Gault formula less than 45 ml/min) at the time of screening.
  Positive testing for HIV, syphilis, hepatitis B and/or C.
  Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification.
  Malabsorption syndrome or other clinically significant gastrointestinal disease that may affect absorption of the study drug (non-correctable vomiting, diarrhea, ulcerative colitis, and others).
  Malignancies in the past medical history.
  Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
  Schizophrenia, schizoaffective disorder, bipolar disorder, or other history of mental pathology or suspicion of their presence at the time of screening.
  Severe, decompensated or unstable somatic diseases (any disease or condition that threaten the patient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).
  Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.
  Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
  Pregnant or nursing women or women planning pregnancy.
  Participation in another clinical study for 3 months prior to inclusion in the study.
  Other conditions that, according to the physician investigator, prevent the patient from being included in the study.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported

• Asymptomatic infection or reinfection
• patients needing oxygen supplementation
• pulse oximetry of oxygenation (SpO2) 10 times of upper normal limit)
• impaired kidney function (creatinine clearance <30 ml/min)
• history of gout or on treatment for gout or hyperuricemia
• malabsorption syndrome
• pregnant or breastfeeding women
• and patients who received interferon or drugs with reported antiviral activity against COVID-19 within 7 days of illness.

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported

• Taking other antivirals (including remdesivir)
• taking steroids (except for a topical or inhaled preparation or the equivalent of >10mg of prednisone) - Beginning in July 2020 with the report of the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, dexamethasone at 6mg daily was permitted
• receiving immune plasma
• or taking immunosuppressive or immunomodulatory drugs (including anticancer drugs, interleukins, interleukin antagonists, or interleukin receptor blockers)
• serious chronic diseases, including moderate or severe hepatic disease, and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic diseases requiring medication dose changes within the last 30 days
• patients with glomerular filtration rates >20mL/min or requiring hemodialysis/continuous ambulatory peritoneal dialysis, liver impairment greater than Child-Pugh A
• uncontrolled psychiatric disease
• or a history of alcohol or drug abuse in the previous 6 months
• requiring mechanical ventilators at entry

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Not reported

• 1. Severe type of disease, with at least one of the following criteria:
  - Frequency of breath > 35 per minute, which does not decrease after the body temperature drops to normal or subfebrile values
• 
  - Blood oxygen saturation (SpO2) < 90% at rest
• 
  - Partial pressure of oxygen in arterial blood (PaO2) < 60 mm Hg
• 
  - Oxygenation index (RaO2/FiO2)? 200 mm Hg
• 
  - Partial pressure of CO2 in arterial blood (PaCO2) < 60 mm Hg
• 
  - Septic shock.
  2. Patients treated with lopinavir/ritonavir, ribavirin, arbidol, chloroquine, hydroxychloroquine, mefloquine, favipiravir within 7 days prior to screening.
  3. Severe cardiovascular diseases currently or 6 months prior to randomization, including: New York Heart Association (NYHA) Class III or IV chronic heart failure, clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction, heart and coronary vessel surgery, significant valvular heart disease, unconarterial hypertension with systolic blood pressure > 180 mm Hg and diastolic blood pressure > 110 mm Hg, pulmonary embolism or deep vein thrombosis.
  4. Severe chronic renal impairment (GFR < 30 ml / min) or continuous renal replacement therapy, hemodialysis or peritoneal dialysis.
  5. A history of cirrhosis or an increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 5 times x upper limit of normal (ULN).
  6. Severe diseases of the central nervous system, including seizures in history or conditions that may lead to their development
• stroke or transient ischemic attack within 12 months prior to screening
• head injuries or loss of consciousness within 12 months prior to screening
• a brain tumor.
  7. Significant uncontrolled concomitant disease, e.g. neurological, renal, hepatic, endocrinological or gastrointestinal disorder which according to the Investigator, could prevent the patient from participating in the study
  8. Malignancies that require chemotherapy within 6 months prior to screening.
  9. Known HIV infection
  10. Hypersensitivity to any component of the study drug.
  11. Participation in other clinical studies or taking other study drugs within 28 days prior to screening.
  12. Pregnant or lactating women or women planning to get pregnant during the clinical study
• women of child-bearing potential (including non-sterilized by surgical means and during the post-menopause period less than 2 years) who do not use adequate contraception methods.
  13. Inability to read or write, unwillingness to understand and follow procedures of study protocol, as well as any other concomitant medical or serious mental conditions that make the patient unfit to participate in the study, limit the legality of obtaining informed consent or can affect patient's ability to participate in the study.

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

No

• (1) Allergic constitution, known to be allergic to baloxavir marboxil or favipiravir or pharmaceutical excipients
• 
  (2) Weight < 40 kg
• 
  (3) Critical illness meeting one of the following conditions: respiratory failure and mechanical ventilation
• shock
• other organ failure requiring ICU monitoring and treatment
• 
  (4) Renal insufficiency (estimated creatinine clearance < 60 ml/min)
• 
  (5) With any of the following laboratory parameter abnormalities detected within 24 hours before screening(according to local laboratory reference range): ALT or AST level > 5 times the upper limit of normal range (ULN) , or ALT or AST level > 3-fold ULN and total bilirubin level > 2-fold ULN
• 
  (6) Base on the researcher's judgment, there are other factors that may cause the subject to be forced to terminate the study midway, such as other serious diseases, serious laboratory examination abnormalities, other factors that affect the safety of the subject or study data and blood sample collection.

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• Severe clinical condition (meeting one of the following criteria: a resting respiratory rate greater than 30 per minute, oxygen saturation below 93%, oxygenation index (OI) < 300 mmHg (1 mmHg = 133.3 Pa), respiratory failure, shock, and/or combined failure of other organs that required ICU monitoring and treatment)
• Chronic liver and kidney disease and reaching end stage. (Serum aspartate aminotransferase (AST) and Serum alanine aminotransferase (ALT) will be elevated over 5 times of normal upper range will excluded) (Normal upper limit of Serum AST = 40 units /L, ALT = 56 units /L)
• Serum uric acid >7.0 mg/dL in Male and Serum uric acid >6.0 mg/dL in Female
• ICU patient
• Previous history of allergic reactions to Favipiravir
• Pregnant or lactating women
• Women of a childbearing age with a positive pregnancy test
• Miscarriage, or within 2 weeks after delivery
• Hypertensive patients, who are taking Calcium Channel Blockers

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Respiratory failure (SpO2≤93%)
• Need for mechanical ventilation at screening
• Severe or extremely severe COVID-19
• Severe lung damage on computed tomography (CT) scans (subtotal diffuse ground-glass induration of pulmonary tissue, the involvement of ≥75% of the lung parenchyma, hydrothorax)
• Unstable hemodynamics
• Any of the following laboratory abnormalities at screening: AST or ALT level >2.5 × upper limit of normal (ULN), platelet count <50 × 109/L

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• Critically ill patients
• patients who had first onset of symptoms/signs suggestive of COVID-19 illness >10 days before randomization
• patients who had allergy or contraindication to the drug, pregnant and lactating mothers
• patients with congestive cardiac failure, moderate to severe hepatic dysfunction or renal failure, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels > 5 times upper limit of normal (ULN) at screening evaluation, serum uric acid higher than the ULN at screening evaluation, those with history of gout or were on current treatment for gout

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing willing stated in the publication:

Yes

• 1) 11 or more days since onset of fever of ≥ 37.5 °C
• 2) the infection episode was a relapse or reinfection
• 3) SpO2<94% without oxygen therapy
• 4) Patients who are pregnant or may be pregnant
• 5) Patients with severe hepatic or renal impairment

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Yes

• Subjects with pneumonia
• In critical condition
• Symptomatic onset >10 days
• Suspected or confirmed to have concurrent or concomitant infections
• Received immunosuppressive treatment
• Received or were on medication with possible SARS-CoV-2 antiviral activity (e.g. interferon alpha, lopinavir, chloroquine, hydroxychloroquine, ivermectin, favipiravir, and remdesivir)
• Pregnant or possibly pregnant
• Lactating

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

Not reported

• Severe infection (defined as need for invasive or non-invasive ventilator support, extracorporeal membrane oxygenation [ECMO] or shock requiring vasopressor support), oxygen saturation ≤93% or arterial oxygen partial pressure or fraction of inspired oxygen of ≤300 mmHg, requiring ICU care for management of ongoing clinical status, inability to take or tolerate oral medications, allergy or hypersensitivity to favipiravir, asthma or chronic obstructive lung disease, severe liver disease (underlying liver cirrhosis or alanine aminotransferase/aspartate aminotransferase elevated over 5 times the upper limit of normal [ULN]), history of gout or hyperuricemia (above the ULN), prolonged QT (defined as QTcF ≥450 msec for men and as QTcF ≥470 msec for women), severely reduced left ventricular function (ejection fraction <30%), or severe renal impairment (creatinine clearance <30 mL/min), or having received continuous renal replacement therapy, hemodialysis or peritoneal dialysis

Protocol

NR

Statistical plan

NR

Data-sharing willing stated in the publication:

No