Publication Ivashchenko AA, Clin Infect Dis, 2020
Funding: Mixed (Russian Direct Investment Fund, the Ministry of Industry and Trade of the Russian Federation, The Skolkovo Innovation Center. )
Multicenter / Russia |
Follow-up duration (days): 29
|Inclusion criteria||The eligible patients included hospitalized men and non-pregnant women of 18 years or older who signed the informed consent form, had moderate PCR-confirmed COVID-19 (positive test at screening), were able to administrate the drug orally and willing to use adequate contraception during the study and 3 months after its completion.|
|Exclusion criteria||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)â¤ 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.
Favipiravir 1800/800mg (1800mg day 1; 800mg days 2-14)
Co-Intervention: Standard care
Duration : 14 days
Favipiravir 1600/600mg (1600mg day 1; 600mg days 2-14)
Co-Intervention: Standard care
Duration : 14 days
60 participants n1=20/ n2=20/ n3=20
|Characteristics of participants|
Mean age : 50.7
Severity : Mild: n=0 / Moderate: n=60/ Severe: n=0 Critical: n=0
|In the register|
rate of viral clearance by Day 5, time to normalization of clinical symptoms (i.e. body temperature), changes on CT scan by Day 15, and incidence and severity of adverse events related to the study drug.
|In the report|
Elimination of SARS-CoV-2 by Day 10 (defined as two negative PCR tests with at least a 24-hour interval)
|Risk of bias
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
|General comment||In addition to all available versions of the pre-print article, the study registry was used in data extraction and risk of bias assessment. The study achieved the target sample size reported in the registry. There is no change from the trial registration in the intervention and control treatments. No protocol or pre-specified statistical analysis plan are available. There is no change from the trial registration in the primary outcomes. Some secondary outcomes in the registry are not present in the report. There was discrepancy in the reported data for mortality and serious adverse events in the preprint and supplementary material. The study is an unblinded, pilot stage, randomized trial and the method used for allocation concealment is not reported.|