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

Lancet eClinical Medicine ^ | 07/16/2021 | Alejandro Krolewiecki, Adrián Lifschitz Matías Moragas Marina Travacio Ricardo Valentini Daniel F.

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Abstract

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.

Research in context

Evidence before this study

The potential role of ivermectin against SARS-CoV-2 was first reported in April 2020 when an Australian group published in-vitro results. Since then, multiple opinion papers and a few studies tried to understand the meaning of those results and utility of ivermectin in COVID-19. Mostly observational reports suggest a potential activity that needs confirmation through randomized controlled trials.

Added value of this study

Our study contributes evidence of the antiviral activity of ivermectin against SARS-CoV-2 in patients with COVID-19 through a randomized, controlled, outcome-assessor blinded clinical trial with innovative analyses that include the use of quantitative viral load determinations and measurement of ivermectin plasma levels, which allow an in-depth interpretation of the data and the identification of ivermectin systemic concentrations needed for a significant antiviral effect. The use of an untreated control group highlights the need for controlled trials and on the viral load dynamics in the natural history of COVID-19. Finally, we also add further information on the safety of high dose ivermectin.

Implications of all the available evidence

A concentration dependent antiviral effect of ivermectin in COVID-19 was identified, with significant reductions in SARS-CoV-2 viral load in respiratory secretions among patients achieving high systemic ivermectin concentration compared to untreated controls. These results, that did not show toxicity related to the use of high dose ivermectin, provide evidence of the antiviral effect and support the design of trials to investigate the clinical implications of our findings. Further exploration of the factors involved in the oral bioavailability of ivermectin are also warranted.

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CLICK THIS LINK FOR THE COMPLETE DESCRIPTION OF THE STUDY

[Truthoverpower]

Silver works against all viruses and bacteria

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Table 1 Baseline characteristic of the study population.

	Control (n = 15)	Ivermectin (n = 30)	P value
Age (year)	38•1 ± 11•7	42•3 ± 12•8	0•29
Gender
Female	5 (33%)	15 (50%)	0•29
Male	10 (67%)	15 (50%)
Weight (kg)	79•7 ± 14•4	75•3 ± 15•0	0•35
Overweight	8 (53%)	6 (20%)	0•05
Obesity I	2 (13%)	11 (37%)	0•20
Obesity II	1 (7%)	1 (3%)	0•79
Obesity III	1 (7%)	1 (3%)	0•79
Oxygen saturation <94%	0	1 (3%)	0•63
Log viral load (log10 copies/reaction)	5•39 ± 1•56 (n = 12)	4•18 ± 1•60 (n = 20)	0•05
Hematology
White blood cell count (cell/µL)	4857 ± 1874	6014 ± 2402	0•09
Lymphocyte count (cell/µL)	1478 ± 266	1744 ± 747	0•09
Biomarkers
Lactate dehydrogenase (IU/L)	460 ± 117	468 ± 140	0•85
Ferritin (mg/dL)	1318 ± 1969	1071 ± 1304	0•66
D-dimer (µg/mL)	1•5 (0•1–2•8)	1•5 (0•5–1•8)	0•82
Time from symptoms onset (day)	3•6 ± 1•4	3•5 ± 1•0	0•78
Body temperature ≥37•5 °C	1 (7%)	4 (13%)	0•70
WHO-ordinal scale
3	13 (87%)	29 (97%)	0•20
4	2 (13%)	1 (3%)
Ground glass opacities in thoracic imaging	6 (40%)	14 (47%)	0•67
Comorbidities
Hypertension	3 (20%)	3 (10%)	0•35
Diabetes	1 (7%)	6 (20%)	0•24
Chronic lung disease/Asthma	1 (7%)	4 (13%)	0•50

Numeric variables are reported as median (IQR) or mean ± standard deviation• Categoric variables are reported as counts (%). Overweight: Body mass index (BMI) 25–29•9 kg/m2; Obesity I: BMI 30–34•9 kg/m2; Obesity II: BMI 35–39•9 kg/m2; Obesity III: BMI >40 kg/m2.

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  Fig. 2 Viral load by quantitative RT-PCR on upper respiratory tract secretions since baseline in patients receiving IVM 0•6 mg/kg/day for 5 days versus untreated controls.

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  Fig. 3: Viral load reduction between baseline and day-5 (median and IQR) in untreated controls and IVM treated patients discriminated by their median IVM plasma concentrations

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  Fig. 4 Viral load decay rates by quantitative RT-PCR on upper respiratory tract secretions in untreated controls and IVM treated patients according to median plasma concentrations of IVM. Data are expressed as median (IQR)

[SeekAndFind]

Ping for your interest

[BrexitBen]

The Fauci/WHO/CDC/CCP coverup cannot sustain itself much longer.

Ivermectin has ALWAYS been the proven, safe, cheap remedy for this Wuhan Virus.

[Kartographer]

So if there is effective treatment WHY DOES ANYONE NEED THE JAB? Because BIG PHARM doesn’t make big bucks off Ivermectin that’s why!!!

[Qiviut]

Just watched a podcast with an excellent discussion on Ivermectin & meta analysis of studies regarding Ivermectin ... Dr. Tess Lawrie & Bret Weinstein (Dark Horse):

https://odysee.com/@BretWeinstein:f/TessLawrie:0

Tess Lawrie is an MD and PHD, external analyst for the World Health Organization, and an expert in analysis of medical evidence

Dark Horse has been demonitized by Youtube so they are posting video on Odysee. This video buffered twice (long buffers, but it came back both times). Lots of complaints in the comments about video (buffering, audio, etc.). Except for the two buffering spots, it played fine for me. I did look on the youtube channel & this video is not there.

[RushIsMyTeddyBear]

Bkmrk

[Mom MD]

The money quote

No differences in clinical evolution at day-7 and day-30 between groups were observed.

[Paladin2]

It’s no Silver bullet, but it does seem to be beneficial [and cheap].

[SeekAndFind]

Actually for me, this IS the money quote:

A concentration dependent antiviral effect of ivermectin in COVID-19 was identified, with significant reductions in SARS-CoV-2 viral load in respiratory secretions among patients achieving high systemic ivermectin concentration compared to untreated controls.

[Jane Long]

Thanks for the link.....bookmarking.

[Jane Long]

👍🏼

[blueplum]

re: log viral load 5•39 ± 1•56 (n = 12) - vs - 4•18 ± 1•60 (n = 20)

is this before or after trials? and were all trial participants alive at day 30 post-first-symptoms? were any rehospitalized since Sept 2020?

At the end of the study the viral load was reduced, but it doesn’t say cleared. Does this mean, as we’ve seen in Brazil, that temporarily reducing but not clearing a viral load, then reexposure, leads to mutations? (similar to the process leading to superbugs)?

[Mom MD]

it may reduce viral load in respiratory secretions but it made no clinical difference according to this study. Clinical abatement of symptoms/improved recovery is the important endpoint not viral loads.

Does ivermectin have some effect? possibly. Even if it does which is not proven yet it has a long way to go to beat monoclonal antibody therapy and steroids. When my elderly family member tested positive ivermectin was not on my radar. Monoclonal antibody therapy and decadron was the only treatment I cared about and made sure happened in a timely fashion

[silverleaf]

So they couldn’t kill people by overdosing them…unlike what they did with HCQ

[TTFX]

Even if it does which is not proven yet it has a long way to go to beat monoclonal antibody therapy and steroids.

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They’re not competing. Mabs can’t be used massively due to cost. It’s not an option to those who can’t access it.

[Mom MD]

It’s pretty available around my area. if not available widely we need to work on it.

[TTFX]

if not available widely we need to work on it.

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While people get that figured out, I suggest people who need something look at Dr Kory’s approach.

[jonrick46]

“In summary, our findings support the hypothesis that IVM has a concentration dependent antiviral activity against SARS-CoV-2 and provides insights into the type of evaluations to be considered in the assessment of antiviral drugs for the control of COVID-19. Follow-up trials to confirm our findings and to identify the clinical utility of IVM in COVID-19 are warranted.”

I looks like ivermectin research is heading to some promising developments:

“Follow-up trials to confirm our findings and to identify the clinical utility of IVM in COVID-19 are warranted.”