A Review of the Clinical Trials Evidence

Base Demonstrating the Efficacy of

Ivermectin in the Prophylaxis and
Treatment of COVID-19
Pierre Kory, MD, MPA
President, Front Line Covid-19 Critical Care Alliance
THE FLCCC ALLIANCE
AGENDA

Conduct a Review of:

The emerging clinical evidence for ivermectin as an effective therapy in
prophylaxis, early, and late hospital disease phases
Disclosures

NONE

Note: All statements and information in this lecture are referenced in our
review manuscript posted on the pre-print server OSF (a final version will
be updated later today at 10.31219/osf.io/wx3zn

4
Prophylaxis Trials Data – 3 RCT’s (n=733), 3 OCT’s (n=1705)
Meta-Analysis of Ivermectin Prophylaxis Studies
Outpatient Trials -5 RCT’s (n=1,287), 4 Case series (n=3,394)
Could it work in Hospitalized Patients and why?
We know that viral replication is either severely diminished or absent
by the time patients enter the hospital

It is the non-viable RNA fragments of

SARS-CoV-2 that provoke an
overwhelming and injurious inflammatory
response
Could it work in Hospitalized Patients and why?

IVERMECTIN appears to have profound anti-inflammatory activity

A growing list of studies are identifying anti-inflammatory mechanisms
Inhibition of cytokine production after lipopolysaccharide exposure
downregulation of transcription of NF-kB (most potent trigger of inflammation)
Limit the production of both nitric oxide and prostaglandin E2
Hospitalized Patients Trials – 6 RCT’s (n=942), 5 OCT’s (n=2,612)
Meta-Analysis of Ivermectin Clinical Studies
Existing Clinical Trials Evidence Base
23 controlled trials including 7,729 patients
 more patients than Oxford’s RECOVERY trial for corticosteroids in COVID-19
 additional five case series including 4,028 patients
14 studies are randomized, controlled trials, n = 2,962
 Approaches the # of patients included in the intervention arm of the RECOVERY trial
9 studies are observational, controlled trials, well-matched comparison groups
11 of the 23 controlled trials have been published in peer-reviewed journals

Prophylaxis trials:
 3 RCT’s with large, statistically significant reductions in transmission rates, N=733 patients
 3 OCT’s with large, statistically significant reductions in transmission rates, N= 1,688
 Existing Clinical Trials Evidence Base
Outpatient Trials
2 RCT’s with large, statistically significant reductions in rates of deterioration or
hospitalization, N=1,085
2 other RCT’s with statistically significant decreases in time to full recovery (one p=.071,
N=130)
1 other RCT with statistically significant decreases in viral load, duration of anosmia and
cough
Hospital Trials
2 RCT’s with large, statistically significant reductions in mortality (N=580)
 1 additional RCT of 140 patients found a reduction in mortality with a p value of… 0.052 (N=140)
3 OCT’s with large, statistically significant reductions in mortality (N=1,688)
 Why isn’t everyone using it? Lets review some
criticisms I have been told:

 “Majority of studies are observational, uncontrolled trials” - FALSE

 all the observational trials have control groups, well matched or propensity matched
 OCT’s and RCT’s have reached similar conclusions throughout the history of evidence-based medicine
 OCT’s are the most ethical approach to studying effective therapies in a pandemic
 “Majority of studies have not been published in peer-reviewed journals” – IRRELEVANT
 11 of the 23 trials have been published in peer-reviewed journals
 Every therapeutic in COVID-19 was adopted from pre-print data prior to peer review
 Remdesivir, corticosteroids, monoclonal antibodies come to mind
 ** Hydroxychloroquine and convalescent plasma were widely adopted before any data supported use
 *** Inoculations of vaccines began.. prior to a pre-print version of the vaccine trial was even available
 “Majority of the trials were performed abroad and are not generalizable to our patients” - ABSURD
 Thus deserves no further comment except to note it’s undercurrent of racism and/or immovable skepticism
 “Majority of the trials were not randomized controlled trials” – FALSE
 14 of the 23 controlled trials were… randomized
CONCLUSION

 The consistency and magnitude of benefit amongst numerous trials of varying designs from
multiple centers and countries around the world is both unique in the history of evidence-
based medicine and supports immediate and widespread adoption.
I have never in my career reviewed and compiled a clinical evidence base for any
medicine or intervention with the reproducibility of study data as I have observed with
ivermectin in the prophylaxis and treatment of COVID-19
This statement applies to the dataset reviewed, without incorporating the powerful
epidemiologic findings by Juan Chamie repeatedly showing population-wide impacts
on case counts and fatality rates in the cities and regions across the world that
initiated ivermectin distribution campaigns during COVID-19
The story of PERU
On May 8th, the national health ministry approved the use of ivermectin by
decree on May 8, 2020, solely based on the invitro study by Caly from
Australia (this recommendation has since changed)
Many regional health ministries began to initiate ivermectin distribution
campaings over the summer
Chamie recently posted a paper on the pre-print server ResearchGate where
he collected and analyzed two critical sets of data from Peru:
He reviewed the media and news reports on the timing and magnitude of each region’s
ivermectin interventions in order to confirm the dates of effective delivery.
He compiled from the Peruvian National databases, data on the mortality and fatality,
in selected age groups over time was
 17

Antiviral Research 2020;178:104787

In Lima, Peru (in red).. No ivermectin distribution campaign took place
 A Tale of Three Cities in Brazil
 Case count decreases in Brazilian cities with ivermectin distribution programs
(yellow rows are cities that distributed ivermectin, neighboring city in same region did not)

Region Confirmed new June July August Population % August

cases/month 2020 (1000) vs. June/July

South Itajaí 2123 2854 998 223 40%

Chapecó 1760 1754 1405 224 80%

North Macapá 7966 2481 2370 503 45%

Ananindeua 1520 1521 1014 535 67%
North East Natal 9009 7554 1590 890 19%
João Pessoa 9437 7963 5384 817 62%
A Tale of Three Cities in Brazil
THE REAL-WORLD EVIDENCE
We must thank the following sources for the clinical and
epidemiologic data:
Juan Chamie, a data analyst from Columbia, now living in the US, has been
compiling and analyzing data from South American countries since April after
first reports of effectiveness of ivermectin in Columbia and Peru
Alan Cannell, a British engineer who lives in Brazil who also stated compiling
data on case counts and deaths in the Brazilian cities that initiated ivermectin
distribution campaigns
TrialSiteNews –for meticulously and immediately posting news of all the
emerging trials evidence reviewed, as well as the work of Chamie and Cannell
above
Paul E. Marik, MD – for getting the FLCCC to focus on ivermectin 
IVERMECTIN: A POTENTIAL GLOBAL SOLUTION?
THE FLCCC has launched a new early treatment protocol around the
core component of ivermectin, called I-MASK+ (www.flccc.net)