Italian-led Ivermectin Meta-Analysis: Is it Time to Consider the Generic Low Cost Option to Help Treat COVID-19? A group of six critical care physicians and researchers, four of who are affiliated with IRCCS (IRCCS Ospedale San Raffaele) San Raffaele Scientific Institute in Milan, Italy, recently conducted a meta-analysis looking into ivermectin and along the way asking a highly uncomfortable question as to whether suspect claims about safety for commonly available drugs in fact are driven by a deep-seated, intensive fear of failure among the scientific and medical community. The idea that, with tens of billions have been invested into a particular approach, anything that gets in the way could be deemed recognition of failure.

 

A group of six critical care physicians and researchers, four of who are affiliated with IRCCS San Raffaele Scientific Institute in Milan, Italy, recently conducted a meta-analysis looking into ivermectin and along the way asking a highly uncomfortable question as to whether suspect claims about safety for commonly available drugs in fact are driven by a deep-seated, intensive fear of failure among the scientific and medical community. After all, tens of billions have been invested into a particular approach and anything that gets in the way could be deemed recognition of failure. In probing the ivermectin situation, the group, including four Italians, a Russian and Spanish doctors and researcher identified over 45 clinical trials ongoing involving ivermectin investigations. In performing yet another ivermectin meta-analysis covering a total of 1323 patients randomized across seven randomized controlled trials conducted in six countries, the group identified that in fact ivermectin treatment led to a statistically significant lower mortality rate when compared to placebo. The authors argue that while in fact “ironclad evidence” represents a fundamental underpinning of modern medicine, in emergency situations the use of an economical medication with a well-known safety profile, including absence of major side effects within dosage ranges, could be considered in fact quite rational. Despite the “urge” to demand large high quality randomized controlled trials, the authors declare that the existing ivermectin studies “point in the same direction” and this simply cannot be ignored. After all, the vaccines are still experimental, meaning they are authorized under emergency use authorization exactly due to conditions associated with pandemic times. Perhaps the authors imply, the same logic could be applied to ivermectin.

The authors shared a few of the studies, including the Bangladesh study led by Ahmed S where treating mild cases of SARS-CoV-2, the study used a dose of ivermectin of 12 mg for 5 days. The results were published in the International Journal of Infectious Diseases.

They also covered the Egyptian study led by Elgazzar A et al covering mild to severe COVID-19, using a dose of 400 mcg/kg (max 24 mg) for 4 days—the results are still in preprint. Yet another study led by Hashim HA in Iraq treated mild to severe cases with 200 mcg/kg for 2 to 3 days and available via the preprint server. Other studies included Niaee, MS et al from Iran, Okumus in Turkey, Ravikirti in India and another study out of Bangladesh authored by Mahmud R.

Critique

Much of the scientific world hasn’t placed much emphasis on ivermectin studies unless they are peer reviewed and authored in respectable medical and scientific journals. While a few groups in the UK and USA have performed similar meta analysis, including the doctors from the Front Line Critical Care COVID-19 Alliance (FLCCC), Dr. Andrew Hill and Dr. Tess Lawrie, as well as an anonymous group that manages a running tally called @CovidAnalysis, common retorts are that these studies aren’t big enough, there is too much variance in design, dosage, etc.

All apex research bodies such as the National Institutes of Health (NIH) select just a few of the ivermectin studies for review, but not all of them. The mainstream media only reports when news is neutral, such as the case of a recent Cali Colombia study that revealed at least in that case the drug didn’t have a statistical impact. See the link for the National Institutes of Health (NIH) COVID-19 Treatment Guidelines for Ivermectin.

About IRCCS San Raffaele Scientific Institute

Four of the six authors are affiliated with IRCCS Ospedale San Raffaele, a university hospital and scientific institute established in 1971 offering specialized care for the most complex health conditions, as well as conduct cutting-edge translational research. This academic medical center takes care of 50,000 inpatients per year, 1,500,000 outpatients and handles 70,000 emergencies a year as well as 30,000 annual surgical interventions. Of course, the study results are not necessarily the opinion of the institution.

The Authors

Pasquale Nardelli, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan Italy

Alberto Zangrillo, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan Italy and Vita-Salute San Raffaele University, Milan, Italy

Gabriele Sanchini, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan Italy

Giovanni Landoni, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan Italy and Vita-Salute San Raffaele University, Milan, Italy

Andrey G Yavorovskiy, IM Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Soledad Romero Garcia, Department of Anaesthesia and Critical Care, Consorcio Hospital General Universitario de Valencia, Valencia, Spain

Call to Action: Physicians and health care professionals should be looking around the world at what different medical professionals, societies and institutes are doing in terms of COVID-19 research. Knowledge is power.

 

HuvePharma Reports Ivermectin Helps Fight Against COVID-19 in Randomized, Controlled, Double-Blind Phase 2 Clinical Trial—Phase 3 Study Next

HuvePharma, a Bulgarian pharmaceutical company, reported on the results of its randomized, double-blind, placebo-controlled Phase2 clinical trial investigating its ivermectin-based product called Huvemek.® The sponsor revealed that the study led to positive results supporting the company to make substantial investment in a Phase 3 clinical trial. This study, reported on recently by TrialSite, showcases yet another study—over 40 now—where the great majority evidence general efficacy and safety when administered in individuals diagnosed with positive COVID-19. Some research-based groups such as BIRD believe the drug is ready now for emergency use authorization. Regardless, Huvepharma completed a Phase 2 clinical trial demonstrating that the drug not only accelerates clearance of the virus (by the third or fourth day after the onset of intake) to significant improvement in patient’s clinical condition as measured by the World Health Organization (WHO) scale. The drug also appears to have anti-inflammatory effects that may offer additional benefit to patients infected with SARS-CoV-2, the virus behind COVID-19.

TrialSite recently reported on this study however with the formal write up published by the sponsor, the pharmaceutical company known as Huvepharma. The sponsor reported that the study drug accelerated the clearance of the virus by day 3 and 4 post treatment start date. The investigators observed marked improvement in patient clinical conditions for those in the study arm based on the WHO-9 category ordinal scale. The study sponsors observed that the ivermectin-based treatment appeared associated with the suppression and normalization of important inflammation biomarkers, considered by many scientists as an important indicator of pathological processes associated with COIVID-19 disease progression—including D-Dimer and C-Reactive Protein (CRP).

Viral Clearance

Day	Huvemek®	Placebo
4th	62%	42%
5th	68%	50%
6th	70%	56%
7th	74%	62%

No Serious Adverse Events

No serious adverse events were associated with this study.

The Sponsor

HuvePharma EooD was the registered sponsor of this study. This diversified pharmaceutical company goes back to its founding in Bulgaria in 1954—see a historical timeline here. The study’s key contact is the company’s Director of Business Development Spas Petkov.

Call to Action: TrialSite will monitor the Phase 3 study when it’s launched. For the study protocol, follow the link.