Antiviral effect of high-dose ivermectin in adults with COVID-19 : A proof-of-concept randomized trial
© 2021 The Author(s)..
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.
| Errataetall: |
ErratumIn: EClinicalMedicine. 2021 Sep;39:101119. - PMID 34462733 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
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Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
EClinicalMedicine - 37(2021) vom: 25. Juli, Seite 100959 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Krolewiecki, Alejandro [VerfasserIn] |
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Date Revised 24.04.2022 published: Electronic-eCollection ClinicalTrials.gov: NCT04381884 ErratumIn: EClinicalMedicine. 2021 Sep;39:101119. - PMID 34462733 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.eclinm.2021.100959 |
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NLM327363290 |
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| 245 | 1 | 0 | |a Antiviral effect of high-dose ivermectin in adults with COVID-19 |b A proof-of-concept randomized trial |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT04381884 | ||
| 500 | |a ErratumIn: EClinicalMedicine. 2021 Sep;39:101119. - PMID 34462733 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2021 The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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