Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial.

Autor:	Krolewiecki A; Instituto de Investigaciones de Enfermedades Tropicales (IIET-CONICET), Sede Regional Orán, Universidad Nacional de Salta, Alvarado 751 (4530), Orán, Argentina., Lifschitz A; Laboratorio de Farmacología, CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Centro de Investigación Veterinaria de Tandil (CIVETAN), Tandil, Argentina., Moragas M; Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan'-CONICET, Ciudad de Buenos Aires, Argentina., Travacio M; Cátedra de Química General e Inorgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina., Valentini R; Departamento de Medicina, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina., Alonso DF; Centro de Oncología Molecular y Traslacional (COMTra) y Plataforma de Servicios Biotecnológicos, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina., Solari R; Hospital Francisco J. Muñiz, Buenos Aires, Argentina., Tinelli MA; Laboratorio Elea/Phoenix, Los Polvorines, Argentina., Cimino RO; Instituto de Investigaciones de Enfermedades Tropicales (IIET-CONICET), Sede Regional Orán, Universidad Nacional de Salta, Alvarado 751 (4530), Orán, Argentina., Álvarez L; Laboratorio de Farmacología, CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Centro de Investigación Veterinaria de Tandil (CIVETAN), Tandil, Argentina., Fleitas PE; Instituto de Investigaciones de Enfermedades Tropicales (IIET-CONICET), Sede Regional Orán, Universidad Nacional de Salta, Alvarado 751 (4530), Orán, Argentina., Ceballos L; Laboratorio de Farmacología, CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Centro de Investigación Veterinaria de Tandil (CIVETAN), Tandil, Argentina., Golemba M; Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan'-CONICET, Ciudad de Buenos Aires, Argentina., Fernández F; Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan'-CONICET, Ciudad de Buenos Aires, Argentina., Fernández de Oliveira D; Departamento de Medicina, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina., Astudillo G; Hospital Francisco J. Muñiz, Buenos Aires, Argentina., Baeck I; Departamento de Medicina, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina., Farina J; Servicio de Infectología, Hospital Cuenca Alta, Cañuelas, Argentina., Cardama GA; Centro de Oncología Molecular y Traslacional (COMTra) y Plataforma de Servicios Biotecnológicos, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina., Mangano A; Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría 'Prof. Dr. Juan P. Garrahan'-CONICET, Ciudad de Buenos Aires, Argentina., Spitzer E; Laboratorio Elea/Phoenix, Los Polvorines, Argentina., Gold S; Fundación Mundo Sano, Buenos Aires, Argentina., Lanusse C; Laboratorio de Farmacología, CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Centro de Investigación Veterinaria de Tandil (CIVETAN), Tandil, Argentina.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2021 Jun 18; Vol. 37, pp. 100959. Date of Electronic Publication: 2021 Jun 18 (Print Publication: 2021).
DOI:	10.1016/j.eclinm.2021.100959
Abstrakt:	Background: There are limited antiviral options for the treatment of patients with COVID-19. Ivermectin (IVM), a macrocyclic lactone with a wide anti-parasitary spectrum, has shown potent activity against SARS-CoV-2 in vitro . This study aimed at assessing the antiviral effect of IVM on viral load of respiratory secretions and its relationship with drug concentrations in plasma. Methods: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviral activity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of care plus oral IVM at 0·6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patients were adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primary endpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitative RT-PCR. Concentrations of IVM in plasma were measured. Study registered at ClinicalTrials.gov: NCT04381884. Findings: 45 participants were recruited (30 to IVM and 15 controls) between May 18 and September 9, 2020. There was no difference in viral load reduction between groups but a significant difference was found in patients with higher median plasma IVM levels (72% IQR 59-77) versus untreated controls (42% IQR 31-73) ( p  = 0·004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r: 0·47, p  = 0·02). Adverse events were similar between groups. No differences in clinical evolution at day-7 and day-30 between groups were observed. Interpretation: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19. Funding: This work was supported by grant IP-COVID-19-625, Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina and Laboratorio ELEA/Phoenix, Argentina. Competing Interests: AK reports grants and lecture fees from Laboratorio Elea/Phoenix and a grant from Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación, Argentina. DFA reports personal fees from Laboratorio ELEA-Phoenix outside the submitted work; RV, RS and JF report personal fees from Elea Phoenix Laboratory during the conduct of the study. MT report personal fees from Elea/Phoenix. MAT and ES are employees of Laboratorios Elea/Phoenix. SG is a member of the Board of Directors of Laboratorio Elea/Phoenix. All other authors declare no competing interests. (© 2021 The Author(s).)
Databáze:	MEDLINE
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