study on safety and clinical efficacy of azvudine in covid-19 patients (sars-cov-2 infected)

Conditions: COVID-19

Summary: estimated number of participants: 342 participants with covid-19 design: phase iii, single-center, randomized, double-blind, parallel, placebo-controlled clinical study. in december 2021, there was a drop in the number of hospitalizations and the cases of copd, tuberculosis and hiv associated with covid-19, which are outside the inclusion criteria of this study. after the initial data of the study, there was a discussion with anvisa and the size of the sample calculation was revised by amendment 4 (180 participants), and the methodology of statistical analysis for a new sample calculation was "a formula for sample calculation for superiority studies using proportions, according to the book do chow et al (chow, s.-c., shao, j., wang, h., \&lokhnygina, y. eds. 2017. sample size calculations in clinical research: third edition, chapman and hall/crc). thus, anvisa concluded that the adjustments are in accordance with the agency's guidelines, approving e4, which was later also approved by the ethics committee.

hypothesis: azvudine has therapeutic potential and safety profile for the treatment of patients infected with sars-cov-2. goals: primary objective • to assess the efficacy and safety of azvudine (fnc) in relation to placebo, in patients infected with sars-cov-2 in moderate to severe stage; secondary objective • to evaluate the clinical outcome of the azvudine group (fnc) compared to the placebo group in patients infected by sars-cov-2 in moderate to severe stage; pharmaceutical form of the experimental medicine: azvudine 1 mg tablets comparators: azvudine placebo statistical planning: the analyzes will be performed by fas, pps and ss and should be stratified by the severity of the disease (moderate, severe) and age (\<60 years, ≥ 60 years), to assess the following parameters: * progression of the disease (moderate to severe, severe type); * negative viral load conversion rate; * time of negative conversion of viral load; * temperature recovery time; * time necessary to improve diarrhea, myalgia, fatigue, and other symptoms; * time to improve the pulmonary image; * frequency of supplemental oxygenation or non-invasive ventilation; * frequency of aes; * mortality rate. all statistical tests will be bilateral tests. if the p value is ≤0.05, it is considered that there is statistical significance between the difference in the tests.

Eligibility criteria:
inclusion criteria: 1. individuals aged 18 or over, regardless of gender; 2. patients hospitalized in moderate to severe stages in line with the ministry of health classification; 3. positive diagnosis for sars-cov-2 by molecular amplification of the virus in rt-pcr diagnosed from a respiratory sample (nasopharynx, oropharyngeal, lower respiratory tract \[eg, sputum\]) collected \<96 hours before randomization; 4. time of onset of symptoms and inclusion ≤ 14 days; 5. internation within 48 hours after inclusion in the study; 6. follow-up availability during the study period; 7. voluntary membership to participate in the study and signing the informed consent form. exclusion criteria: 1. patients known or suspected of being sensitive to azvudine or excipients (inactive ingredients: microcrystalline cellulose, hydrated lactose, polyvinylpyrrolidone k30, croscarmellose sodium, magnesium stearate); 2. patients diagnosed with pneumonia caused by other pathogens; 3. patients with liver disease (total bilirubin ≥2 times above the normal limit, alt / tgp and ast / tgo ≥5 times above the normal limit) 4. patients with renal failure (glomerular filtration rate ≤60ml / min / 1.73 m2) or are receiving continuous renal replacement therapy, hemodialysis or peritoneal dialysis; 5. individuals with malabsorption syndrome, or other conditions that affect gastrointestinal absorption, and circumstances in which patients need intravenous nutrition, or cannot take drugs orally or nasogastrically; 6. pregnant or lactating women, or women with the potential to become pregnant during the study period and within 6 months after the end of administration; 7. patients already included in other clinical trials; 8. patient under treatment for hiv; 9. patients being treated with other antivirals (eg lopinavir / ritonavir, remdesivir, umifenovir / arbidol, favipiravir, interferon-α) 10. patients undergoing treatment with monoclonal antibodies (eg tocilizumab and sarilumab / kevzara); 11. patients who are on a clinical treatment plan that includes the concomitant administration of any other experimental treatment or off-label use of drugs already on the market (eg hydroxychloroquine sulfate; 12. patients who require invasive mechanical ventilation or extracorporeal membrane oxygenation (ecmo) at the time of randomization; 13. any clinically significant medical condition or medical history that, in the investigator's opinion, might discourage participation in the study.

Keywords: azvudine sars-cov-2 covid-19 fnc