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Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19 | |
Erwin Chiquete Liz Toapanta-Yanchapaxi Carlos Cantú-Brito | |
Acceso Abierto | |
Atribución-NoComercial-SinDerivadas | |
https://doi.org/10.1101/2020.04.26.20079988 | |
https://www.medrxiv.org/content/10.1101/2020.04.26.20079988v1 | |
Introduction Coronavirus disease 2019 (COVID-19) is the systemic entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may cause death through severe atypical pneumonia and acute lung injury. Valproic acid (VPA) has shown anti-inflammatory activity and mild intrinsic antiviral effect. These properties warrant the study of VPA as a possible active treatment in persons with severe COVID-19. Methods Consecutive adult patients needing invasive mechanical ventilation (IMV) will be given intravenous (i.v.) VPA at a starting dose of 20 mg/kg/day and up to 60/kg/day (in 60 min i.v. infusions in 250 mL normal saline) as needed to reach plasma VPA concentrations of 50–100 μg/mL (measured every 72 h). These patients will be followed-up for 10 days for the primary outcome and for a further period of 30 days after treatment completion for the secondary outcome of recurrence. The primary study outcome is the reduction in the case fatality rate of at least 50% after 10 days of treatment (as compared with natural history). Secondary outcomes are the reduction of length of stay (LOS) of at least 50%, as well as COVID-19 recurrence at 30-day follow-up. The most important safety outcomes are acute liver failure, acute pancreatitis, and thrombocytopenia. Conclusion Although long-term adverse effects and even pro-inflammatory consequences have been reported with the chronic use of VPA, given the urgent need for a drug against COVID-19 to shorten the high mortality and LOS, the study of VPA is justified from a scientific standpoint. | |
bioRxiv | |
01-05-2020 | |
Preimpreso | |
Inglés | |
Público en general | |
VIRUS RESPIRATORIOS | |
Versión publicada | |
publishedVersion - Versión publicada | |
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