Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hos
Ivermectin is an FDA-approved broad spectrum anti-parasitic agent, which was initially approved in humans in 1987 to treat onchocerciasis, awarding the discoverers the Nobel prize of Medicine in 2015. Its main activity was known for therapy against infections caused by roundworm parasites. Over the years, the spectrum was extended and included also parasitic skin infections such as scabies among others. 
In the last decade, several in-vitro studies have shown its anti-viral activity against a broad range of viruses, mainly RNA viruses including HIV, influenza and several flaviviruses such as Dengue virus (DENV), Zika, and West Nile Virus.[2-6] Recently ivermectin was tested in vitro against SARS-CoV-2 and showed ∼5000-fold reduction (99.8%) in viral RNA after 48 hours. However, it was criticized that the dosing used in the study cannot be achieved with the current approved dose.
Study design A randomized controlled, double blinded trial to evaluate the effectiveness of ivermectin in reduction of viral shedding among mild to moderate COVID-19 patients. The study was conducted in hotels located in (Tel-Aviv, Jerusalem and Ashkelon) Israel, that have been designated as isolation facilities for mild to moderate COVID-19 patients, not requiring oxygen. Institutional Review Board (IRB) approval was given by the Sheba Medical Center’s IRB (7156/20). Written informed consent was received from each participating individual before recruitment.
Study population Patients were eligible for enrollment in the study if they were 18 years of age or older; not pregnant; with molecular confirmation of COVID-19 by RT-PCR; and with the intention to receive results within the first three days from symptoms onset. However due to the delay (three to four days) in getting results in the community, we extended the time up to seven days from symptoms onset. Since our main outcome was the change in viral shedding (as reflected by Ct value), asymptomatic cases were also included within 5 days from molecular diagnosis. Patients were excluded if they weighed below 40kg, were with known allergy to the drugs, unable to take oral medication, participating in another RCT for treatment of COVID-19. In addition, patients who had RT-PCR results with Ct (cycle threshold) value >35 in first two consecutive were excluded. Patients with comorbidities of cardiovascular disease, diabetes, chronic respiratory disease (excluding mild intermittent asthma), hypertension, and or cancer were defined as high-risk patients.
Randomization Randomization in a 1:1 ratio was done by computer-generated program using randomization.com (http://www.jerrydallal.com/random/randomize.htm) by Clinical Research Coordinator (CRC), blinded to the rest of the study team. This CRC was not requiting patients and the numbered pills bottles were available only for the physician who were requiting. Patients assigned to the intervention arm received ivermectin in a dosage regimen according to body weight; patients weighing between 40-69 kg received four tablets (=12mg) daily and patients weighing ≥70kg received five tablets (=15mg) daily, all for three days. Patients assigned to the placebo arm received the same number and same appearance of pills per weight daily, for three days. They were guided to take the pills one hour before a meal. The investigators and patients were blinded to the assignment.
Clinical Presentation Among the study population 83% were symptomatic. The most common symptoms, fatigue, fever, cough, headache, and myalgia were prevalent in approximately half of the study population. (symptoms detailed in Table S1-supplement). None of these variables were statistically different between the two study arms.
Study Outcome Viral load during the study period is depicted in Figure 2. Viral load of the ivermectin group decreased faster in comparison to the placebo group at the early stage of the intervention, during days two to six. As spontaneous recovery takes place also in the placebo group the viral load is decreasing, having similar viral load since day eight.
Kaplan-Meier analysis (Figure 3) adjusted to symptom onset showed the significant difference between the ivermectin and placebo arms during the course of treatment.
credited to medrxiv