Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial

Abstract

Background Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. Methods A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. Results None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. Conclusions At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.

The selective effect of Ivermectin on different human coronaviruses; in-vitro study

“…Regarding the effect of the drug in reducing viral load, our clinical study on the effect of three days of ivermectin in reducing the viral load in mild cases of ambulatory patients showed its advantage over placebo in a double-blind randomized control study 50 . Similar results were obtained in a study in Mexico demonstrating a significant decline on day 5 51 , while other studies did not find any advantage of the drug 52 "The main argument against using ivermectin is that the level of existing evidence for its positive effect is based mainly on studies lacking a high standard of rigorous methodology 53,54 .…”

Ivermectin for treatment of COVID-19: A systematic review and meta-analysis

“…Seventeen of the thirty-three studies reported on MV requirement (n = 6049 participants) [ 10 , [24] , [25] , [26] , 59 , 60 , 64 , 65 , [68] , [69] , [70] , [71] , [72] , 75 , 76 , 81 , 82 ], and significant difference was observed between the two groups (RR 0.67, 95% CI 0.47–0.96, I 2 = 0%; Fig. 3 ).…”

“…COVID-19 disease severity was asymptomatic/mild in 12 randomized controlled trials, moderate in 1, mild and moderate in 17, severe in 2, and moderate and severe in 1. Studies were done in 19 countries: Argentina (n = 3 studies) [ [58] , [59] , [60] ], Bangladesh (n = 2) [ 61 , 62 ], Brazil (n = 1) [ 10 ], China (n = 1) [ 63 ], Colombia (n = 1) [ 64 ], Egypt (n = 3) [ 23 , 65 , 66 ], India (n = 3) [ [67] , [68] , [69] ], Iran (n = 3) [ 26 , 70 , 71 ], Israel (n = 1) [ 72 ], Italy (n = 1) [ 22 ], Japan, (n = 1) [ 73 ], Malaysia (n = 1) [ 24 ], Mexico (n = 2) [ 74 , 75 ], Nigeria (n = 1) [ 76 ], Pakistan (n = 2) [ 77 , 78 ], Spain (n = 1) [ 79 ], Thailand (n = 2) [ 25 , 80 ], Turkey (n = 1) [ 81 ], and USA (n = 3) [ 21 , 82 , 83 ]. Of all 33 studies, 7 had an overall high risk of bias, 13 had some concerns of bias, and 13 had a low risk ( Supplementary Fig.…”

“…Med. Iran (n = 1158) 0.4 mg/kg per day for 3 days + SOC Placebo + SOC Moderate in 53.9%, severe in 46.1% 44.9 (5–96) 100 52.6 50 7.7 20.1 18.7 Clinical improvement, Recovery, LOS, ICU admission, MV requirement, AEs, Mortality 7 ND Rocha et al (2022) [ 75 ] BMC Infect. Dis.…”

“…Twenty-nine of the thirty-three studies reported on all-cause mortality rate (n = 8738 participants) [ 10 , [21] , [22] , [23] , [24] , [25] , [26] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] ]. There was no significant difference in all-cause mortality rate between IVM and controls (RR 0.95, 95% CI 0.75–1.21, I 2 = 0%; Fig.…”