Pierre Kory, MD1*, G. Umberto Meduri, MD2†, Jose Iglesias, DO3, Joseph Varon, MD4,
Keith Berkowitz, MD5, Howard Kornfeld, MD6, Eivind Vinjevoll, MD7, Scott Mitchell, MBBS8,
Fred Wagshul, MD9, Paul E. Marik, MD10
1 St. Luke’s Aurora Medical Center, Milwaukee, WI.
2 Univ. of Tennessee Health Science Center, Memphis, TN.
3 Hackensack School of Medicine, Seton Hall, NJ.
4 University of Texas Health Science Center, Houston, TX.
5 Center for Balanced Health, New York
6 Recovery Without Walls
7 Volda Hospital, Volda, Norway
8 Princess Elizabeth Hospital, Guernsey, UK
9 Lung Center of America, Dayton, Ohio
10 Eastern Virginia Medical School
*Correspondence to: email@example.com
†Dr. Meduri’s contribution is the result of work supported with the resources and use of facilities at
the Memphis VA Medical Center. The contents of this commentary do not represent the views of the
U.S. Department of Veterans Affairs or the United States Government
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 2 / 28
In March 2020, an expert panel called the Front Line COVID-19 Critical Care Alliance (FLCCC) was
created and led by Professor Paul E. Marik with the goal of continuously reviewing the rapidly
emerging basic science, translational, and clinical data in order to gain insight into and develop a
treatment protocol for, COVID-19. At the same time, many centers and groups employed a multitude
of novel therapeutic agents empirically and within clinical trials, often during inappropriate time
points during this now well-described multi-phase disease. Either as a result of these frequent trial
design failures or due to the lack of sufficient anti-viral or anti-inflammatory properties, nearly all
trialed agents have proven ineffective in reducing the mortality of COVID-19. Based on a recent
series of negative published therapeutic trial results, in particular the SOLIDARITY trial, this virtually
eliminates any treatment role for remdesivir, hydroxychloroquine, lopinavir/ritonavir, interferon,
convalescent plasma, tocilizumab, and mono-clonal antibody therapy.
Despite the growing list of failed therapeutics in COVID-19, the FLCCC recently discovered that
ivermectin, an anti-parasitic medicine, has highly potent real-world, anti-viral, and anti-inflammatory
properties against SARS-CoV-2 and COVID-19. This conclusion is based on the increasing study
results reporting effectiveness, not only within in-vitro and animal models, but also in numerous
clinical trials from centers and countries around the world. Repeated, consistent, large magnitude
improvements in clinical outcomes have now been reported when ivermectin is used not only as a
prophylactic agent but also in mild, moderate, and even severe disease states from multiple, large,
randomized and observational controlled trials. Further, data showing impacts on population wide
health outcomes have resulted from multiple large “natural experiments” that appear to have occurred
when various regional health ministries and governmental authorities within South American
countries initiated “ivermectin distribution” campaigns to their citizen populations in the hopes the
drug would prove effective. The tight, reproducible, temporally associated decreases in case counts
and case fatality rates in each of those regions compared to nearby regions without such campaigns,
suggest that ivermectin is proving to be a global solution to the pandemic. This is now further
evidenced by the recent incorporation of ivermectin as a prophylaxis and treatment agent for COVID-
19 in the national treatment guidelines of Egypt as well as the state of Uttar Pradesh in Northern India,
populated by 210 million people.
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 3 / 28
To our knowledge, the current review is the earliest to compile sufficient clinical data to demonstrate
a strong signal of therapeutic efficacy based on numerous clinical trials in multiple disease phases,
however it is limited by the fact that only a minority of studies have been published in peer-reviewed
publications, with the majority of results compiled from manuscripts uploaded to medicine pre-print
servers or from registered trials that have posted preliminary results on clinicaltrials.gov. Therefore, it
is imperative that our major national and international health care agencies be made aware of this
emerging data in order to devote the necessary resources to more quickly validate these studies and
confirm the major, positive epidemiologic impacts that have been recorded when ivermectin is widely
distributed among populations with a high incidence of COVID-19 infections.
One Sentence Summary
Review of recently available clinical trial results demonstrating efficacy of ivermectin in prophylaxis
and treatment of COVID-19.
In March 2020, an expert panel called the Front Line COVID-19 Critical Care Alliance (FLCCC) was
created and led by Professor Paul E. Marik. The group of expert critical care physicians and thought
leaders immediately began continuously reviewing the rapidly emerging basic science, translational,
and clinical data in COVID-19 which then led to the early creation of a treatment protocol for hospitalized
patients called MATH+, based on the collective expertise of the group in both the research and
treatment of multiple other severe infections causing lung injury (1).
Two manuscripts reviewing the scientific rationale and evolving published clinical evidence
base in support of the MATH+ protocol passed peer review and have been accepted for publication in
major medical journals at two different time points in the pandemic (2, 3). The most recent paper,
currently in production, reports a 6.1% hospital mortality rate in COVID-19 patients measured in the
two U.S hospitals that systematically adopted the MATH+ protocol, a markedly decreased mortality
rate compared to the 23.9% hospital mortality rate calculated from a review of 39 studies including
over 165,000 patients (unpublished data; available on request). For a review of the therapeutic interventions
comprising the current MATH+ protocol, see Table 1 below.
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 4 / 28
Table 1. MATH+ Hospital Treatm ent Protocol for COVID-19
MATH+ Hospital Treatment Protocol for COVID-19 (www.flccc.net)
Medication Indication/Initiation Recommended dosing Titration/Duration
Methylprednisolone A. Mild hypoxemia:
requires O2 via NC to
maintain saturation > 92%
40 mg IV bolus
then 20 mg IV twice daily
A1. Once off O2, then taper with 20 mg daily
x 3 days then 10 mg daily x 3 days, monitor
A2. If FiO2, or CRP increase move to B.
hypoxemia (High Flow O2,
COVID-19 Respiratory Failure protocol
(see Figure 2)
Preferred: 80 mg IV bolus, followed by
80 mg / 240 ml normal saline IV infusion
at 10 ml/hr
Alternate: 40 mg IV twice daily
B1. Once off IMV, NPPV, or High flow O2, decrease
to 20 mg twice daily. Once off O2, then taper
with 20 mg/day for 3 days then 10 mg/day for
B2. If no improvement in oxygenation in 2–4 days,
double dose to 160 mg/daily.
B3. If no improvement and increase in CRP/Ferritin,
move to “Pulse Dose” below.
C. Refractory Illness/
“Pulse” dose with 125 mg IV
every 6–8 hours
Continue for 3 days then decrease to 80 mg IV/daily
dose above (B). If still no response or CRP/Ferritin
high/rising, consider “Salvage Therapy” below
Ascorbic Acid O2 < 4 L on hospital ward 500–1000 mg oral every 6 hours Until discharge
O2 > 4 L or in ICU 1.5–3 g intravenously every 6 hours Sooner of 7 days or discharge from ICU, then switch
to oral dose above
Thiamine ICU patients 200 mg IV twice daily Sooner of 7 days or discharge from ICU
Heparin (LMWH) Hospital ward patients
on ≤ 4 L O2
0.5 mg/kg twice daily
Monitor anti-Xa, target 0.2–0.5 IU/ml
Until discharge then start DOAC at half dose
for 4 weeks
ICU patients or > 4 L O2 1 mg/kg twice daily
Monitor anti-Xa levels, target 0.6–1.1 IU/ml
Later of: discharge from ICU or off oxygen,
then decrease to hospital ward dosing above
(should be considered
a core medication)
Upon admission to hospital
0.2 mg/kg – days 1 and 3 Repeat – days 6 and 8 if not recovered
Vitamin D Hospital ward patients
on ≤ 4 L O2
0.532 mg PO day 1, then 0.266 mg PO day 3
and 7 and weekly thereafter
10,000 IU/day PO or 60,000 IU day 1,
30,000 IU days 3 and 7 and then weekly
Until discharge from ICU
ICU patients or on > 4 L O2 Cholecalciferol 480,000 IU (30 ml) PO on
admission, then check Vitamin D level on
day 5, if < 20 ng/ml, 90,000 PO IU/day for
Until discharge from ICU
Atorvastatin ICU Patients 80 mg PO daily Until discharge
Melatonin Hospitalized patients 6–12 mg PO at night Until discharge
Zinc Hospitalized patients 75–100 mg PO daily Until discharge
Famotidine Hospitalized Patients 40–80 PO mg twice daily Until discharge
Patients refractory to
pulse dose steroids
5 sessions, every other day Completion of 5 exchanges
Legend: CRP = C-Reactive Protein, DOAC = direct oral anti-coagulant, ICU = Intensive Care Unit, IMV = Invasive Mechanical Ventilation, IU = International units, IV = intravenous,
NIPPV = Non-Invasive Positive Pressure Ventilation, O2 = oxygen, PO (per os) = oral administration
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 5 / 28
Although the adoption of MATH+ has been considerable, it largely occurred only after the
RECOVERY and other trials were published which supported one of the main components (corticosteroids)
of the combination therapy approach created at the onset of the pandemic (4–9). Despite the
plethora of supportive evidence, the MATH+ protocol for hospitalized patients has not yet become
widespread. Further, the world is in a worsening crisis with the potential of again overwhelming
hospitals and ICU’s. As of November 10th, 2020, the number of deaths attributed to COVID-19 in the
United States reached 245,799 with over 3.7 million active cases, the highest number to date (10).
Multiple European countries have now begun to impose new rounds of restrictions and lockdowns (11).
Further compounding these alarming developments was a wave of recently published negative
results from therapeutic trials done on medicines thought effective for COVID-19, that now virtually
eliminate any treatment role for remdesivir, hydroxychloroquine, lopinavir/ritonavir, interferon, convalescent
plasma, tocilizumab, and mono-clonal antibody therapy, particularly in later phases (12–17).
One year into the pandemic, the only therapy considered “proven” as an effective treatment in
COVID-19 is the use of corticosteroids in patients with moderate to severe illness (18). Similarly most
concerning is the fact that little has proven effective to prevent disease progression to prevent
Despite this growing list of failed therapeutics in COVID-19, it now appears that ivermectin, a
widely used anti-parasitic medicine with known anti-viral and anti-inflammatory properties is proving
a highly potent and multi-phase effective treatment against COVID-19. Although much of the trials
data supporting this conclusion is available on medical pre-print servers or posted on clinicaltrials.gov,
most have not yet undergone peer-review. Despite this limitation, the FLCCC expert panel, in their
prolonged and continued commitment to reviewing the emerging medical evidence base, and considering
the impact of the recent surge, has now reached a consensus in recommending that ivermectin
for both prophylaxis and treatment of COVID-19 should be systematically and globally adopted.
The FLCCC recommendation is based on the following set of conclusions derived from the existing
data, which will be comprehensively reviewed below:
1) Since 2012, multiple in-vitro studies have demonstrated that Ivermectin inhibits the replication
of many viruses, including influenza, Zika, Dengue and others (19–27).
2) Ivermectin inhibits SARS-CoV-2 replication, leading to absence of nearly all viral material by
48h in infected cell cultures (28).
3) Ivermectin has potent anti-inflammatory properties with in-vitro data demonstrating profound
inhibition of both cytokine production and transcription of nuclear factor-κB (NF-κB), the
most potent mediator of inflammation (29–31).
4) Ivermectin significantly diminishes viral load and protects against organ damage in multiple
animal models when infected with SARS-CoV-2 or similar coronaviruses (32, 33).
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 6 / 28
5) Ivermectin prevents transmission and development of COVID-19 disease in those exposed to
infected patient (34–36,54).
6) Ivermectin hastens recovery and prevents deterioration in patients with mild to moderate
disease treated early after symptoms (37–42,54).
7) Ivermectin hastens recovery and avoidance of ICU admission and death in hospitalized
8) Ivermectin reduces mortality in critically ill patients with COVID-19 (43,45,54).
9) Ivermectin leads to striking reductions in case-fatality rates in regions with widespread use
10) The safety, availability, and cost of ivermectin is nearly unparalleled given its near nil drug
interactions along with only mild and rare side effects observed in almost 40 years of use and
billions of doses administered (49).
11) The World Health Organization has long included ivermectin on its “List of Essential
Following is a comprehensive review of the available efficacy data as of November 8, 2020, taken
from in-vitro, animal, clinical, and real-world studies all showing the above impacts of ivermectin in
In-vitro and animal studies of ivermectin activity against SARS-CoV-2
Since 2012, a growing number of cellular studies have demonstrated that ivermectin has anti-viral
properties against an increasing number of RNA viruses, including influenza, Zika, HIV, Dengue, and
most importantly, SARS-CoV-2 (19-27). Caly et al first reported that ivermectin significantly inhibits
SARS-CoV-2 replication in a cell culture model, observing the near absence of all viral material 48h
after exposure to ivermectin (28). Insights into the mechanisms of action by which ivermectin both
interferes with the entrance and replication of SARS-CoV-2 within human cells are mounting.
Researchers report high binding activity to the SARS-CoV-2 spike protein thereby limiting binding to
the ACE-2 receptor and preventing cellular entry of the virus (51). Ivermectin has also been shown to
bind to or interfere with multiple essential structural and non-structural proteins required by the virus
in order to replicate (51, 52) . Finally, ivermectin also binds to the SARS-CoV-2 RNA-dependent
RNA polymerase (RdRp), thereby inhibiting viral replication (53).
Arevalo et al investigated in a murine model infected with a type 2 family RNA coronavirus
similar to SARS-CoV-2, (mouse hepatitis virus), the response to 500 mcg/kg of ivermectin vs.
placebo (32). The study included 40 infected mice, with 20 treated with ivermectin, 20 with phosphate
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 7 / 28
buffered saline, and then 16 uninfected control mice that were also given phosphate buffered saline.
At day 5, all the mice were euthanized to obtain tissues for examination and viral load assessment.
The 20 non-ivermectin treated infected mice all showed severe hepatocellular necrosis surrounded by
a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load
(52,158 AU), while in the ivermectin treated mice a much lower viral load was measured (23,192 AU;
p<0.05), with only few livers in the ivermectin treated mice showing histopathological damage such
that the differences between the livers from the uninfected control mice were not statistically significant.
Dias De Melo and colleagues recently posted the results of a study they did with golden
hamsters that were intranasally inoculated with SARS-CoV-2 virus, and at the time of the infection,
the animals also received a single subcutaneous injection of 0.4mg/kg ivermectin. Control animals
received only the physiologic solution (33). They found the following among the ivermectin treated
hamsters; a dramatic reduction in anosmia (33.3% vs 83.3%, p=.03) which was also sex-dependent in
that the male hamsters exhibited a reduction in clinical score while the treated female hamsters failed
to show any sign of anosmia. They also found significant reductions in cytokine concentrations in the
nasal turbinate’s and lungs of the treated animals despite the lack of apparent differences in viral titers.
Exposure prophylaxis studies of ivermectin’s ability to prevent transmission of
Data is also now available showing large and statistically significant decreases in the transmission of
COVID-19 among human subjects based on data from three randomized controlled trials (RCT) and
one retrospective observational study (OCT); however, none of the studies have been peer-reviewed
yet (34–36,54). The largest RCT was posted on the Research Square pre-print server on November 13,
2020 while the two other RCT’s have submitted data to clinicaltrials.gov, which then performed a
quality control review and posted the results. The OCT was posted on the pre-print server medRxiv on
November 3, 2020 (34).
The largest RCT by Elgazzar and colleagues at Benha University in Egypt randomized 200
health care and households contacts of COVID-19 patients where 100 patients took a high dose of
0.4mg/kg on day 1 and repeated the dose on day 7 in addition to wearing personal protective equipment
(PPE), while the control group of 100 contacts wore PPE only (54). There was a large and
statistically significant reduction in contacts tesing positive by RT-PCR when treated with ivermectin
vs. controls, 2% vs 10%, p<.05.
The second largest RCT, conducted in Egypt by Shouman et al. at Zagazig University,
included 340 (228 treated, 112 control) family members of patients positive for SARS-CoV-2 via
PCR (35). Ivermectin, (approximately 0.25mg/kg) was administered twice, on the day of the positive
test and 72 hours later (35). After a two-week follow up, a large and statistically significant decrease
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 8 / 28
in COVID-19 symptoms among household members treated with ivermectin was found, 7.4% vs.
58.4%, p<.001. Similarly, in another RCT conducted by Carvallo et al. in Argentina involving 229
healthy citizens, 131 were randomized to treatment with 0.2mg of ivermectin drops taken by mouth
five times per day (34). After 28 days, none of those receiving ivermectin prophylaxis group had
tested positive for SARS-COV-2 versus 11.2% of patients in the control arm (p<.001). In a much
larger follow-up randomized controlled trial by the same group included 1,195 health care and they
found that over a 3 month period, there were no infections recorded among the 788 workers that took
weekly ivermectin prophylaxis while 58% of the 407 controls had become ill with COVID-19. This
study demonstrates that perfect protection against transmission can be achieved among high-risk
health care workers by taking 12mg once weekly (90). More recently, in a large retrospective
observational case-control study from India, Behara et al. reported that among 186 case-control pairs
(n=372) of health care workers, they identified 169 participants that had taken some form of
prophylaxis, with 115 that had taken ivermectin prophylaxis (n=38 of the COVID-19 cases and n=77
of the controls) (36). After matched pair analysis, they reported that in the workers who had taken two
dose ivermectin prophylaxis, the odds ratio for contracting COVID-19 was markedly decreased (0.27,
95% CI, 0.15–0.51). Notably, one dose prophylaxis was not found to be protective in this study.
Based on both their study finding and the Egyptian prophylaxis study, the All India Institute of
Medical Sciences included a consensus statement in the manuscript recommending health care
workers take two 0.3mg/kg doses of ivermectin 72 hours apart and to repeat the dose monthly.
A fascinating study on the protective role of ivermectin in nursing home residents in France
was recently published which found that in a facility that suffered a scabies outbreak, all 69 residents
and 52 staff were treated with ivermectin (87). During the time period surrounding this event, 7/69
residents fell ill with COVID-19 (10.1%). In this group with an average age of 90 years, only one
resident required oxygen support and no resident died. In a matched control group of residents from
surrounding facilities, they found 22.6% of residents fell ill and 4.9% died.
The most definitive evidence was published recently in the International Journal of Anti-
Microbial agents where a group of researchers analyzed data using the prophylactic chemotherapy
databank administered by the WHO along with case counts obtained by Worldometers, a public data
aggregation site used by among others, the Johns Hopkins University (89). When they compared the
data from countries with active ivermectin mass drug administration programs for the prevention of
parasite infections, they discovered that the COVID-19 case counts in these countries were
significantly lower, to a high degree of statistical significance, p<.001.
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 9 / 28
Figure 1. Meta-analysis of ivermectin prophlaxis trials
Further data supporting a role for ivermectin in decreasing transmission rates can be found from South
American countries where, in retrospect, large “natural experiments” appear to have occurred. For
instance, beginning as early as May, various regional health ministries and governmental authorities
within Peru, Brazil, and Paraguay initiated “ivermectin distribution” campaigns to their citizen populations.
In one such example from Brazil, the cities of Itajai, Macapa, and Natal distributed massive
amounts of ivermectin doses to the city’s population, where, in the case of Natal, 1 million doses were
distributed (36). The data in Table 2 below was compiled on September 14, 2020 and was obtained
from the official Brazilian government site (https://covid.saude.gov.br) and the national press
consortium by an engineer named Alan Cannel whose findings were published on the website
TrialSiteNews and are thus not peer-reviewed.
Table 2. Comparison of case count decreases among Brazilian cities with and without ivermectin distribution
campaigns (bolded cities distributed ivermectin, neighboring regional city below did not)
Region Confirmed new
June July August Population
% Cases in
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%
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 10 / 28
Similar examples of temporally associated declines in case counts and death rates in regions that
undertook ivermectin distribution campaigns are rapidly emerging and will be discussed in more
Clinical studies on the efficacy of ivermectin in treating mildly ill outpatients
Currently, six studies which include a total of over 3,000 patients with mild outpatient illness have
been completed, a set comprised of 4 RCT’s and three case series (38–41,45,46,57). Of the RCTs, the
smallest one by Podder et al. was peer-reviewed and published, two RCTs have been posted on preprint
servers, and the largest RCT passed quality control review and the data is now available on
The largest RCT by Mahmud et al. was conducted in Dhaka, Bangladesh and targeted 400
patients with 363 patients completing the study (39). In this study, as in many other of the clinical
studies to be reviewed, either a tetracycline (doxycycline) or macrolide antibiotic (azithromycin) was
included as part of the treatment. The importance of including antibiotics such as doxycycline or
azithromycin is unclear, however, both tetracycline and macrolide antibiotics have recognized antiinflammatory,
immunomodulatory, and even antiviral effects (58–61). Although the posted data from
this study does not specify the amount of mildly ill outpatients vs. hospitalized patients treated,
important clinical outcomes were profoundly impacted, with increased rates of early improvement
(60.7% vs. 44.4% p<.03) and decreased rates of clinical deterioration (8.7% vs 17.8%, p<.013). Given
that mildly ill outpatients mainly comprised the study cohort, only two deaths were observed (both in
the control group).
Another RCT by Hashim et al. in Baghdad, Iraq included 140 patients equally divided; the
control group received standard care, the treated group included a combination of both outpatient and
hospitalized patients (45). In the 96 patients with mild-to-moderate outpatient illness, they treated 48
patients with a combination of ivermectin/doxycycline and standard of care and compared outcomes
to the 48 patients treated with standard of care alone. The standard of care in this trial included many
elements of the MATH+ protocol, such as dexamethasone 6mg/day or methylprednisolone 40mg
twice per day if needed, Vitamin C 1000mg twice/day, Zinc 75–125mg/day, Vitamin D3 5000 IU/day,
azithromycin 250mg/day for 5 days, and acetaminophen 500mg as needed. Although no patients in
either group progressed or died, the time to recovery was significantly shorter in the ivermectin
treated group (6.3 days vs 13.7 days, p<.0001).
Another RCT of ivermectin treatment in 116 outpatients was recently posted on the pre-print
server Research Square by Chowdhury et al. in Bangladesh (57). In this trial they compared a group of
60 patients treated with the combination of ivermectin/doxycycline to a group of 60 patients treated
with hydroxychloroquine/doxycycline with a primary outcome of time to negative PCR. Although
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 11 / 28
they found no difference in this outcome, in the treatment group, the time to symptomatic recovery
approached statistical significance (5.9 days vs. 7.0 days, p=.07). In another smaller RCT of 62
patients by Podder et al., they also found a shorter time to symptomatic recovery that approached
statistical significance (10.1 days vs 11.5 days, p>.05, 95% CI, 0.86 – 3.67) (56).
Morgenstern et al. in the Dominican Republic reported a case series of 2,688 consecutive
symptomatic outpatients seeking treatment in the emergency room, the majority of whom were
diagnosed using a clinical algorithm. The patients were treated with high dose ivermectin of 0.4mg/kg
for one dose along with five days of azithromycin. Only 16 of the 2,688 patients (0.59%) required
subsequent hospitalization with one death recorded (42).
In another case series of 100 patients by Mushed et al. in Bangladesh, all treated with a combination
of 0.2mg/kg ivermectin and doxycycline, they found that no patient required hospitalization
nor died, and all patients symptoms improved within 72 hours (37).
Finally, in a case series from Argentina by Carvallo et al., they reported on a combination
protocol called IDEA which used ivermectin, aspirin, dexamethasone and enoxaparin. In the 135 mild
illness patients, all survived (38).
Clinical studies of the efficacy of ivermectin in hospitalized patients
Studies of ivermectin amongst more severely ill hospitalized patients include 4 RCT’s, 4 OCTs, and a
database analysis study (40,41,43–45,54,63,67,68). Two of the OCTs and one RCT are published in
major medical journals, with the two RCTs and one OCT and the database analysis posted on preprint
The largest RCT in hospitalized patients, was performed concurrent with the prophylaxis study
reviewed above by Elgazzar et al (54). 400 patients were randomized amongst 4 treatment groups of
100 patients each. Groups 1 and 2 included mild/moderate illness patients only, with Group 1 treated
with one dose 0.4mg/kg ivermectin plus standard of care (SOC) and Group 2 received
hydroxychloroquine (HCQ) 400mg twice on day 1 then 200mg twice daily for 5 days plus standard of
care. There was a statistically significant lower rate of progresson in the ivermectin treated group (1%
vs. 22%, p<.001) with no deaths and 4 deaths respectivtly. Groups 3 and 4 all included only severely
ill patients, with group 3 again treated with single dose of 0.4mg/kg plus SOC while Group 4 received
HCQ plus SOC. In this severely ill subgrop, the differences in outcomes was even larger, with again
lower rates of progression 4% vs. 30%, and 2% vs 20% mortality (p<.001).
The one largely outpatient RCT done by Hashim reviewed above also included 22 hospitalized
patients in each group. In the ivermectin/doxycycline treated group, there were 11 severely ill patients
and 11 critically ill patients while in the standard care group, only severely ill patients (n=22) were
included due to their ethical concerns of including critically ill patients in the control group (45). This
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 12 / 28
decision led to a marked imbalance in the severity of illness between these hospitalized patient
groups. However, despite the mismatched severity of illness between groups and the small number of
patients included, beneficial differences in outcomes were seen, but not all reached statistical significance.
For instance, there was a large reduction in the rate of progression of illness (9% vs. 31.8%,
p = 0.15) and, most importantly, there was a large difference in mortality amongst the severely ill
groups which reached a borderline statistical significance, (0% vs 27.3%, p =.052). Another important
finding was the surprisingly low mortality rate of 18% found among the subset of critically ill
patients, all of whom were treated with ivermectin.
A recent RCT from Iran was posted on the pre-print server Research Square on November 24,
2020 again showing a dramatic reduction in mortality with ivermetin use (63). Among multiple
ivermectin treatment arms (different ivermectin dosing strategies were used in the intervention arms),
the average mortality was reported as 3.3% while the average mortality within the standard care and
placebo arms was 18.8%, with an OR of 0.18 (95% CI 0.06-055, p<.05).
Spoorthi and Sasanak performed a prospective RCT of 100 hospitalized patients whereby they
treated 50 with ivermectin and doxycycline while the 50 controls were given a placebo consisting of
Vitamin B6 (44). Allthough no deaths were reported in either group, the ivermectin treatment group
had a shorter hospital LOS 3.7 days vs 4.7 days, p=.03, and a shorter time to complete resolution of
symptoms, 6.7 days vs 7.9 days, p=.01.
The largest OCT in hospitalized patients was done by Rajter et al. at Broward Health Hospitals
in Florida and which was recently published in the major medical journal Chest (43). They performed
a retrospective OCT on 280 consecutive treated patients and compared those treated with ivermectin
to those without. 173 patients were treated with ivermectin (almost all with a single dose) while 107
were not. In both unmatched and propensity matched cohort comparisons, similar, large, and statistically
significant lower mortality was found amongst ivermectin treated patients (15.0% vs. 25.2%,
p=.03). Further, in the subgroup of patients with severe pulmonary involvement, mortality was
profoundly reduced when treated with ivermectin (38.8% vs. 80.7%, p =.001).
Another large OCT by Khan et al. in Bangladesh compared 115 pts treated with ivermectin to
a standard care cohort consisting of 133 patients (40). Despite a significantly higher proportion of
patients in the ivermectin group being male (i.e. with well-described, lower survival rates in COVID),
the groups were otherwise well matched, yet the mortality decrease was statistically significant (0.9%
vs. 6.8%, p<.05) (64–66). The largest OCT is a study from Brazil that was published in the form of a
brief letter to the editor by Portman-Baracco et al (67). Although the primary data was not provided,
they reported that in 704 hospitalized patients treated with a single dose of 0.15mg/kg ivermectin
compared to 704 controls, overall mortality was reduced (1.4% vs. 8.5%, HR 0.2, 95% CI 0.12–0.37,
p<.0001). Similarly, in the patients on mechanical ventilation, mortality was also reduced (1.3% vs.
7.3%). A small study by Gorial et al. from Baghdad, Iraq recently posted on the pre-print server
medRxiv, compared 16 ivermectin treated patients to 71 controls (41). This study also reported a
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 13 / 28
significant reduction in length of hospital stay (7 days vs. 13 days, p<.001) in the ivermectin group.
The case series by Carvallo using the IDEA protocol, which included ivermectin, reported a 3.1%
mortality rate amongst the 32 hospitalized patients treated (38).
One retrospective analysis of a database of hospitalized patients compared responses in
patients receiving ivermectin, azithromycin, hydroxychloroquine or combinations of these medicines.
In this study, no benefit for ivermectin was found, however the treatment groups in this analysis all
included a number of patients who died on day 2, while in the control groups no early deaths
occurred, thus the comparison appears limited (68).
Anti-inflammatory properties of ivermectin supporting efficacy in late phase
The evidence for the anti-viral activity of ivermectin from the in-vitro and animal studies is consistent
with and supportive of the efficacy demonstrated in the above prophylactic and early treatment trials;
however, the large, beneficial impacts reviewed in the preceding section on hospitalized and ICU
patient populations suggest that the potent anti-inflammatory properties of ivermectin also play a
major role. This assumption is based on the fact that little viral replication is occurring in the later
phases of COVID-19, nor can virus be cultured, and only in a minority of autopsies can viral
cytopathic changes be found (69-71). Given the general lack of viral presence or cytopathic activity
late in the disease course, this supports the finding by Li et al. that it is the non-viable RNA fragments
of SARS-CoV-2 that lead to the high mortality and morbidity in COVID-19 via the provocation of an
overwhelming and injurious inflammatory response (72). Based on these insights, it appears that the
increasingly well described in-vitro properties of ivermectin as an inhibitor of inflammation are far
more clinically potent than previously recognized. The growing list of studies demonstrating the antiinflammatory
properties of ivermectin include its ability to; inhibit cytokine production after
lipopolysaccharide exposure, downregulate transcription of NF-kB, and limit the production of both
nitric oxide and prostaglandin E2 (29-31).
Summary of the clinical evidence base for ivermectin against COVID-19
The below meta-analysis includes the mortality data from the OCTs and RCTs separately (Figure 2).
The consistent and reproducible signals leading to an overall statistically significant mortality benefit
from within both study designs is remarkable, especially given that in several of the studies treatment
was initiated late in the disease course.
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 14 / 28
Figure 2. Meta-analysis of mortality outcomes reported from clinical trials of ivermectin in COVID-19
OBS = observational controlled trial, RCT = Randomized controlled Trial
A detailed summary of each trial which comprised the previously reviewed clinical evidence base can
be found in Table 3 below:
Table 3. Summary of clinical studies assessing the efficacy of ivermectin in COVID-19
AUTHOR, COUNTRY, SOURCE STUDY DESIGN,
IVERMECTIN DOSE DOSE FREQUENCY CLINICAL OUTCOMES
Prophylaxis Trials % Ivermectin vs. % Controls
Shouman W, Egypt
members of pts
40–60 kg: 15 mg
60–80 kg: 18 mg
> 80 kg: 24 mg
Two doses, 72
7.4% vs. 58.4%
Carvallo H, Argentina
0.2 mg drops 1 drop five times a
day x 28 days
0.0% vs. 11.2%
Elgazzar A, Egypt
Health care and
contacts of pts
0.4 mg/kg Two doses, Day 1
and Day 7
2% vs. 10% tested
positive for COVID-19
Carvallo H. Argentina
12 mg Once weekly for up
to ten weeks
0.0% of the 788 workers
taking ivermectin vs. 48%
of the 407 controls
Bernigaud C. France
Annales de Dermatologie et de Venereologie
N=69 case control
0.2 mg/kg Once 10.1% vs. 22.6% residents
0.0% vs 4.9% mortality
Behera P, India
N=186 case control
0.3 mg/kg Day 1 and Day 4 2 doses reduced odds of
(OR 0.27 95% CI 0.16–
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 15 / 28
AUTHOR, COUNTRY, SOURCE STUDY DESIGN,
IVERMECTIN DOSE DOSE FREQUENCY CLINICAL OUTCOMES
Clinical Trials – Hospitalized Patients
Elgazzar A, Egypt
0.4 mg/kg Once Moderate Illness
worsened (1% vs 22%,
p<.001. Severe illness
worsened 4% vs 30%,
mortality 2% vs 20%,
Niaee S. M.
0.2, 0.3, 0.4 mg/kg
(3 dosing strategies)
Once vs. Days 1,3,5 Mortality 3.3% vs. 18.3%.
OR 0.18, (.06-0.55)
Hashim H, Iraq
1/3 hospital pts
0.2 mg/kg +
Daily for 2–3 days Recovery time 6.3 vs 13.6
days (p<.001), 0% vs
27.3% mortality in
severely ill (p=.052)
Spoorthi S, India
AIAM, 2020; 7(10):177–182
Once Shorter Hospital LOS, 3.7
vs. 4.7 days, p=.03, faster
resolution of symptoms,
6.7vs 7.9 days, p=.01
Ahmed S. Dhaka, Bangladesh
International Journal of Infectious Disease
12mg Daily for 5 days Faster viral clearance 9.7
vs 12.7 days, p=.02
Portman-Baracco A, Brazil
Arch Bronconeumol. 2020
0.15 mg/kg Once Overall mortality 1.4% vs.
8.5%, HR 0.2, 95% CI
Soto-Beccerra P, Peru
Unknown dose <48hrs
Unknown No benefits found
Rajter JC, Florida
0.2 mg/kg +
Day 1 and Day 7 if
Overall mortality 15.0%
vs. 25.2%, p=.03, Severe
illness mortality 38.8 vs.
Khan X, Bangladesh
Arch Bronconeumol. 2020
12 mg Once on admission Mortality 0.9% vs. 6.8%,
p<.05, LOS 9 vs. 15 days,
Gorial FI, Iraq
0.2 mg/kg +
HCQ and azithromycin
Once on admission LOS 7.6 vs. 13.2, p<.001,
0/15 vs. 2/71 died
Camprubi D. Spain
0.2mg/kg Once, median of 12
symptom onset (8-
Discharged by Day 8:
53.8% vs. 46.1% – NS
Mortality 15.4% vs 23.1%
Clinical Trials – Outpatients
Mahmud R, Bangladesh
12 mg +
Once, within 3 days
of PCR+ test
Early improvement 60.7%
vs. 44.4%, p<.03,
deterioration 8.7% vs
Chowdhury A, Bangladesh
Outpatients 0.2 mg//kg +
Once Recovery time 5.93 vs
9.33 days (p=.071)
Podder CS, Bangladesh
IMC J Med Sci 2020;14(2)
Outpatients 0.2 mg/kg Once Recovery time 10.1 vs
11.5 days (NS), average
time 5.3 vs 6.3 (NS)
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 16 / 28
AUTHOR, COUNTRY, SOURCE STUDY DESIGN,
IVERMECTIN DOSE DOSE FREQUENCY CLINICAL OUTCOMES
Morgenstern J, Dominican Republic
0.3 mg/kg x 1 dose
Mortality = 0.03% in 2688
outpatients, 1% in 300
patients, 30.6% in 111
Carvallo H, Argentina
Days 0 and 7 All 135 with mild illness
survived, 1/32 (3.1% of
hospitalized patients died
Alam A, Bangladesh, J of Bangladesh College
Phys and Surg, 2020;38:10-15
Outpatients 0.2 mg/kg +
Once All improved within 72
HCQ = hydroxychloroquine, NS = non-significant OCT = observational controlled trial, RCT = randomized controlled Trial
Epidemiological data showing impacts of widespread ivermectin use on
population case counts and case fatality rates
Similar to the individual cities in Brazil that measured large decreases in case counts soon after
distributing ivermectin in comparison to neighboring cities without such campaigns, in Peru, the
government approved the use of ivermectin by decree on May 8, 2020, solely based on the in-vitro
study by Caly et al. from Australia (46,73). Soon after, multiple state health ministries initiated
ivermectin distribution campaigns in an effort to decrease what was at that time some of the highest
COVID-19 morbidity and mortality rates in the world. In a recent paper posted to the preprint server
Research Square by a data analyst named Juan Chamie, two critical sets of data were compiled and
compared; first he reviewed the reports on the timing and magnitude of each regions ivermectin
interventions via a review of official communications, press releases, and the Peruvian Situation
Room database in order to confirm the dates of effective delivery, and second, data on the mortality
and fatality in selected age groups over time was compiled from the registry of the National Computer
System of Deaths (SINADEF), and from the National Institute of Statistics and Informatics (46). With
these data, he was then able to compare the timing of major decreases in both excess deaths and case
fatality rates among 8 states in Peru with the initiation dates of their respective ivermectin distribution
campaigns as shown in Figure 3 below. Excess deaths were calculated by comparison to death rates at
the same time in the 3 years prior to the COVID-19 pandemic. The analysis was restricted solely to
patients over 60 in order to remove any confounding due to increases in infections amongst healthier
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 17 / 28
Figure 3. Decreases in total deaths/population and COVID-19 case incidences in the over 60 population
among eight Peruvian states after deploying mass ivermectin treatment
Figure 4 below from the same study presents data on the case fatality rates in patients over 60, again
among the 8 states in Peru. Note the dramatically decreased case fatality rates among older patients
with COVID-19 after ivermectin became widely distributed in those areas.
Figure 4. Case fatality rate decreases among patients over 60 in eight Peruvian states after deploying mass
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 18 / 28
The reduced mortality rates achieved throughout Peru can also be seen from the analysis of the three
Brazilian cities reviewed above, shown in Table 4 below.
Table 4. Change in death rates among neighboring regions in Brazil
(bolded regions contained a major city that distributed Ivermectin to its citizens, the other regions did not)
REGION STATE % CHANGE IN AVERAGE DEATHS/
WEEK COMPARED TO 2 WEEKS PRIOR
South Santa Catarina –36 2,529 35.6
PARANÁ –3 3,823 35.3
Rio Grande do Sul –5 4,055 33.4
North Amapá –75 678 80.2
AMAZONAS –42 3,892 93.9
Pará 13 6,344 73.7
North East Rio Grande do Norte –65 2,315 66.0
CEARÁ 62 8,666 95.1
Paraíba –30 2,627 65.4
Another compelling example can be seen from the data compiled from Paraguay, again by Chamie,
who noted that the government of the state of Alto Parana had launched an ivermectin distribution
campaign in early September. Although the campaign was officially described as a “de-worming”
program, this was interpreted as a guise by the regions governor to avoid reprimand or conflict with
the National Ministry of Health that recommended against use of ivermectin to treat COVID-19 in
Paraguay (74). The program began with a distribution of 30,000 boxes of ivermectin and by October
15, the governor declared that there were very few cases left in the state as can be seen in Figure 5
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 19 / 28
Figure 5. Paraguay – COVID-19 case counts and deaths in Alto Parana (blue) after Ivermectin distribution
began (bolded blue line) compared to other departments (48,76).
Ivermectin in Post-COVID-19 Syndrome
Increasing reports of persistent, vexing, and even disabling symptoms after recovery from acute
COVID-19 have been reported and which many have termed the condition as “long Covid” and
patients as “long haulers”, estimated to occur in approximately 10% of cases (77–79). Generally
considered as a post-viral syndrome consisting of a chronic and sometimes disabling constellation of
symptoms which include, in order, fatigue, shortness of breath, joint pains and chest pain. Many
patients describe their most disabling symptom as impaired memory and concentration, often with
extreme fatigue, described as “brain fog”, and are highly suggestive of the condition myalgic
encephalomyelitis/chronic fatigue syndrome, a condition well-reported to begin after viral infections,
in particular with Epstein-Barr virus. Although no specific treatments have been identified for long
COVID, a recent manuscript by Aguirre-Chang et al from the National University of San Marcos in
Peru reported on the experience with ivermectin in such patients (80). They treated 33 patients who
were between 4 and 12 weeks from the onset of symptoms with escalating doses of ivermectin;
0.2mg/kg for 2 days if mild, 0.4mg/kg for 2 days if moderate, with doses extended if symptoms
persisted. They found that in 87.9% of the patients, resolution of all symptoms was observed after
two doses with an additional 7% reporting complete resolution after additional doses. Their
experience suggests the need for controlled studies to better test efficacy in this vexing syndrome.
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History and safety of ivermectin
The discovery of Ivermectin in 1975 was awarded the 2015 Nobel Prize in Medicine given its global
impact in reducing onchocerciasis (river blindness), lymphatic filiariasis, and scabies in endemic areas
of central Africa, Latin America, India and Southeast Asia (81). It has since been included on the
WHO’s “List of Essential Medicines.” Beyond the massive, global reductions in morbidity and
mortality achieved in many low-and middle-income populations, the knowledge base establishing its
high margin of safety and low rate of adverse effects is nearly unparalleled given it is based on the
experience of billions of doses dispensed. In one example, The Meztican (ivermectin) Donation
Program established in 1987 to combat river blindness in over 33 countries provided more than 570
million treatments in its first 20 years alone (81). Numerous studies report low rates of adverse events,
with the majority mild, transient, and largely attributed to the body’s inflammatory response to the
death of the parasites and include itching, rash, swollen lymph nodes, joint paints, fever and headache
(49). In a study which combined results from trials including over 50,000 patients, serious events
occurred in less than 1% and largely associated with administration in Loa loa (82). Further, according
the pharmaceutical reference standard Lexicomp, the only medications contraindicated for use with
ivermectin are the anti-tuberculosis and cholera vaccines while the anticoagulant warfarin would
require dose monitoring. A longer list of drug interactions can be found on the drugs.com database,
with nearly all interactions leading to a possibility of either increased or decreased blood levels of
ivermectin. Given studies showing tolerance and lack of adverse effects in human subjects given
escalating high doses of ivermectin, toxicity is unlikely although a reduced efficacy due to decreased
levels may be a concern (83).
Currently, as of November 27, 2020, it appears that, based on the data from the in-vitro,
animal, prophylaxis, clinical, safety, and large scale epidemiologic analyses demonstrating decreases
in both case counts and fatality rates in regions with widespread ivermectin use, the anti-parasitic drug
ivermectin should be considered a highly effective regional and global solution to the COVID-19 pandemic.
A concern with this interpretation and conclusion is that, as was detailed above, many of these
trial results have not yet passed peer review and that 5 of the 15 clinical trials were conducted using an
observational design. To address the former concern, it is hoped that the journals to which the study
manuscripts have been submitted will undertake an expedited review due to the critical importance of
those studies in providing the world the appropriate level of scientific evidence required to undertake
a potentially major shift in public health policy against this pandemic.
In regards to the misplaced concerns over the soundness of observational trial findings, it must
be recognized that in the case of ivermectin; 1) the majority of the trials employed a randomized,
controlled trial design (10 of the 15 reviewed above), and 2) that observational and randomized trial
designs reach equivalent conclusions on average in nearly all diseases studied, as reported in a large
Cochrane review of the topic from 2014 (84). In particular, OCTs that employ propensity-matching
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 21 / 28
techniques (as in many of the above trials), find near identical conclusions to later-conducted RCTs in
many different disease states, including coronary syndromes, critical illness, and surgery (85–87).
Despite these repeated findings of equivalence between study designs, the authors recognize
that, at times, there are situations where multiple OCTs may conclude a benefit of a specific intervention,
while multiple, repeated RCTs do not. In such situations where the entirety of the study design
conclusions conflict, it can be assumed that one of the sets of trial designs contain a systematic bias,
un-identified confounder, or “fatal flaw” in execution (i.e. frequent delayed therapy in RCTs, especially
in critical illness states), thus it should not be automatically assumed that such confounders or
biases exist only within OCTs. Thus, expert interpretation of trial design and data in these situations
must prevail. However, as evidenced in the current review, meta-analysis, and summary table, all of
the various study design conclusions on ivermectin efficacy strongly align in the same direction and
magnitude. Thus, in such a situation, it is imperative that health policy makers and academics avoid
the non-evidence based practice of repeatedly dismissing findings from OCTs while over-emphasizing
the need for placebo-controlled RCTs, given that such practices, most acutely in this pandemic, have
caused harm in patient outcomes when treated with placebo. RCTs are best reserved for medicines
with high risk, high cost, and/or a truly indeterminate efficacy. To study medicines that are cheap,
safe, and widely available with a long track record of use and an existing favorable efficacy or benefit/
risk ratio, well-conducted OCTs, particularly those employing propensity matching, are not only
scientifically valid but most consistent with widely agreed-upon ethical principles, especially in a
pandemic. All must consider Declaration 37 of the World Medical Association’s “Helsinki Declaration
on the Ethical Principles for Medical Research Involving Human Subjects,” first established in
1964, which states:
In the treatment of an individual patient, where proven interventions do not exist or other
known interventions have been ineffective, the physician, after seeking expert advice, with
informed consent from the patient or a legally authorized representative, may use an unproven
intervention if in the physician’s judgement it offers hope of saving life, re-establishing
health or alleviating suffering. This intervention should subsequently be made the object of
research, designed to evaluate its safety and efficacy. In all cases, new information must be
recorded and, where appropriate, made publicly available.
In keeping with the above principle, if a physician believes, based on the current body of evidence
presented above, that it is far more likely that ivermectin will help rather than harm, it would be
unethical to either withhold treatment or to treat with a placebo. However, in such cases, especially if
treatment with ivermectin should become widespread, it is imperative that data on clinical outcomes
and safety continue to be meticulously collected and expertly analyzed. In keeping with the robust and
emerging evidence reviewed above, the Front Line COVID-19 Critical Care Alliance recently created
a prophylaxis and early treatment approach for COVID-19 called “I-MASK+”. This protocol includes
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 22 / 28
ivermectin as a core therapy in both early treatment and prophylaxis of both high-risk patients and
post-exposure to household members with COVID-19 (Tables 5 and 6). The Front Line COVID-19
Critical Care Alliance is committed to measuring outcomes in those treated with ivermectin and reviewing
all emerging results from the current and any future clinical trials of ivermectin in COVID-19.
In summary, based on the existing and cumulative body of evidence, we recommend the use of
ivermectin in both prophylaxis and treatment for COVID-19. In the presence of a global COVID-19
surge, the widespread use of this safe, inexpensive, and effective intervention could lead to a drastic
reduction in transmission rates as well as the morbidity and mortality in mild, moderate, and even
severe disease phases.
Table 5. I-MASK+ Prophylaxis & Early Outpatient Treatment Protocol for COVID-19
MEDICATION RECOMMENDED DOSING
lvermectin Prophylaxis for high risk individuals: 0.2 mg/kg* dose on day 1 and day 3, then one dose/month
Post COVID-19 exposure prophylaxis**: 0.2 mg/kg dose on day 1 and day 3
Vitamin D3 1,000–3,000 IU/day
Vitamin C 1,000 mg twice daily
Quercetin 250 mg/day
Melatonin 6 mg before bedtime (causes drowsiness)
Zinc 50 mg/day of elemental zinc
EARLY OUTPATIENT TREATMENT PROTOCOL***
MEDICATION RECOMMENDED DOSING
lvermectin 0.2 mg/kg x 1 dose on day 1 and day 3
Vitamin D3 4,000 IU/day
Vitamin C 2,000 mg 2–3 times daily and Quercetin 250 mg twice a day
Melatonin 10 mg before bedtime (causes drowsiness)
Zinc 100 mg/day elemental zinc
Aspirin 325 mg/day (unless contraindicated)
* Example for a person of 50 kg body weight: 50 kg × 0.15 mg = 7.5 mg (1 kg = 2.2 lbs)= 2.5 tablets (3mg/tablet). See table 6 for
weight-based dose calculations
** To use if a household member is COVID-19 positive, or if you have had prolonged exposure to a COVID-19+ patient without
wearing a mask
*** For late phase – hospitalized patients – see the FLCCC’s “MATH+” protocol on www.flccc.net
f Take on an empty stomach with water
Review of the Emerging Evidence Supporting the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19[FLCCC Alliance; Updated Dec. 7, 2020] 23 / 28
Table 6. Suggested Ivermectin Dose by Body Weight for Prophylaxis and Treatment of COVID-19
Conversion (1kg=2.2 lbs)
(doses calculated per
upper end of weight range)
(0.2 mg/kg= 0.09mg/lb)
(Each tablet = 3 mg; doses rounded
to nearest half tablet above )
70–90 lb 32–40 kg 8 mg (3 tablets=9 mg)
91–110 lb 41–50 kg 10 mg (3.5 tablets)
111–130 lb 51–59 kg 12 mg (4 tablets)
131–150 lb 60–68 kg 13.5 mg (4.5 tablets)
151–170 lb 69–77 kg 15 mg (5 tablets)
171–190 lb 78–86 kg 16 mg (5.5 tablets)
191–210 lb 87–95 kg 18 mg (6 tablets)
211–230 lb 96–104 kg 20 mg (7 tablets=21 mg)
231–250 lb 105–113 kg 22 mg (7.5 tablets=22.5 mg)
251–270 lb 114–122 kg 24 mg (8 tablets)
271–290 lb 123–131 kg 26 mg (9 tablets =27 mg)
291–310 lb 132–140 kg 28 mg (9.5 tablets=28.5 mg)
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List of Tables
Table 1. MATH+ hospital treatment protocol for COVID-19
Table 2. Comparison of case count decreases among Brazilian cities with and without ivermectin
distribution campaigns (bolded cities distributed ivermectin, neighboring regional city below did
Table 3. Summary of clinical studies assessing the efficacy of ivermectin in COVID-19
Table 4. Change in death rates among neighboring regions in Brazil
(bolded regions contained a major city that distributed Ivermectin to its citizens, the neighboring
region did not)
Table 5. I-MASK+ Prophylaxis & early outpatient treatment protocol for COVID-19
Table 6. Suggested ivermectin dose by body weight for prophylaxis and treatment of COVID-19
List of Figures
Fig. 1. Meta-analysis of ivermectin prophylaxis trials
Fig. 2. Meta-analysis of mortality outcomes reported from clinical trials of ivermectin in COVID-19
Fig. 3. Decreases in total deaths/population and COVID-19 case incidences in the over 60 population
among eight Peruvian states after deploying mass ivermectin treatment
Fig. 4. Case fatality rate decreases among patients over 60 in eight Peruvian states after deploying mass
Fig. 5. Paraguay – COVID-19 case counts and deaths in Alto Parana (blue) after Ivermectin distribution
began (bolded blue line) compared to other departments (48,76).
Pierre Kory: conceptualization, writing, review and editing, visualization. G. Umberto Meduri: writing, review
and editing, investigation. Joseph Varon: review and editing, supervision Jose Iglesias: writing, review and
editing. Eivind Vinjevol: investigation, visualization. Scott Mitchell: review and editing. Howard Kornfeld:
conceptualization, investigation. Fred Wagshul: investigation. Paul E. Marik: conceptualization, formal
analysis, investigation, review and editing, supervision
Data and Materials Availability
All data are is available in the main text or the supplementary materials