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

KROLEWIECKI, ALEJANDRO; LIFSCHITZ, ADRIÁN; MORAGAS, MATÍAS; TRAVACIO, MARINA; VALENTINI, RICARDO; ALONSO, DANIEL F.; SOLARI, RUBÉN; TINELLI, MARCELO A.; CIMINO, RUBÉN O.; ÁLVAREZ, LUIS; FLEITAS, PEDRO E.; CEBALLOS, LAURA; GOLEMBA, MARCELO; FERNÁNDEZ, FLORENCIA; FERNÁNDEZ DE OLIVEIRA, DIEGO; ASTUDILLO, GERMAN; BAECK, INÉS; FARINA, JAVIER; CARDAMA, GEORGINA A.; MANGANO, ANDREA; SPITZER, EDUARDO; GOLD, SILVIA; LANUSSE, CARLOS

EClinicalMedicine

Elsavier

Año: 2021 vol. 37

2589-5370

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 secretionsand its relationship with drug concentrations in plasma.Methods: Proof-of-concept, pilot, randomized, controlled, outcome-assessor blinded trial to evaluate antiviralactivity of high-dose IVM in 45 COVID-19 hospitalized patients randomized in a 2:1 ratio to standard of careplus oral IVM at 0¢6 mg/kg/day for 5 days versus standard of care in 4 hospitals in Argentina. Eligible patientswere adults with RT-PCR confirmed SARS-CoV-2 infection within 5 days of symptoms onset. The primaryendpoint was the difference in viral load in respiratory secretions between baseline and day-5, by quantitativeRT-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 inpatients with higher median plasma IVM levels (72% IQR 5977) versus untreated controls (42% IQR 3173)(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-30between groups were observed.Interpretation: A concentration dependent antiviral activity of oral high-dose IVM was identified at a dosingregimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinicalutility of IVM in COVID-19.