Abstract: EClinicalMedicine 37 (2021) 100959
Contents lists available at ScienceDirect
EClinicalMedicine
journal homepage: https://www.journals.elsevier.com/eclinicalmedicine
Research paper
Antiviral effect of high-dose ivermectin in adults with COVID-19: A proofof-concept randomized trial
n Lifschitzb, Matías Moragasc, Marina Travaciod,
Alejandro Krolewieckia,*, Adria
e
n Solarig, Marcelo A. Tinellih, Rube
n O. Ciminoa,
Ricardo Valentini , Daniel F. Alonsof, Rube
b
ndezc,
, Pedro E. Fleitasa, Laura Ceballosb, Marcelo Golembac, Florencia Ferna
Luis Alvarez
e
g
e
i
s Baeck , Javier Farina ,
ndez de Oliveira , German Astudillo , Ine
Diego Ferna
Georgina A. Cardamaf, Andrea Manganoc, Eduardo Spitzerh,1, Silvia Goldj,1, Carlos Lanusseb,1
a
n, Universidad Nacional de Salta, Alvarado 751 (4530), Ora
n,
Instituto de Investigaciones de Enfermedades Tropicales (IIET-CONICET), Sede Regional Ora
Argentina
b
Laboratorio de Farmacología, CONICET-CICPBA-UNCPBA, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, Cenn Veterinaria de Tandil (CIVETAN), Tandil, Argentina
tro de Investigacio
c
Unidad de Virología y Epidemiología Molecular, Hospital de Pediatría ''Prof. Dr. Juan P. Garrahan''-CONICET, Ciudad de Buenos Aires, Argentina
d
nica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Catedra de Química General e Inorga
e
n Medica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
Departamento de Medicina, Centro de Educacio
f
gicos, Departamento de Ciencia y Tecnología, Universidad Nacional
Centro de Oncología Molecular y Traslacional (COMTra) y Plataforma de Servicios Biotecnolo
de Quilmes, Buenos Aires, Argentina
g
~ iz, Buenos Aires, Argentina
Hospital Francisco J. Mun
h
Laboratorio Elea/Phoenix, Los Polvorines, Argentina
i
~ uelas, Argentina
Servicio de Infectología, Hospital Cuenca Alta, Can
j
n Mundo Sano, Buenos Aires, Argentina
Fundacio
A R T I C L E
I N F O
Article History:
Received 22 February 2021
Revised 17 May 2021
Accepted 25 May 2021
Available online 18 June 2021
A B S T R A C T
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 SARSCoV-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 5977) versus untreated controls (42% IQR 3173)
(p = 0¢004). Mean..
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