Safety and Efficacy of a MEURI Program for the Use of High Dose Ivermectin in COVID-19 Patients

Abstract

BackgroundIn the absence of antiviral alternatives, interventions under research for COVID-19 might be offered following guidelines from WHO for monitored emergency use of unregistered and experimental interventions (MEURI). Ivermectin is among several drugs explored for its role against SARS-CoV-2, with a well-known safety profile but conflicting data regarding clinical utility for COVID-19. The aim of this report is to inform on the results of a MEURI Program of high-dose ivermectin in COVID-19 carried out by the Ministry of Health of the Province of La Pampa, Argentina.MethodsCOVID-19 subjects, within 5 days of symptoms onset were invited to participate in the program, which consisted in the administration of ivermectin 0.6 mg/kg/day for 5 days plus standard of care. Active pharmacosurveillance was performed for 21 days, and hepatic laboratory assessments were performed in a subset of patients. Frequency of Intensive Care Unit (ICU) admission and COVID-19-related mortality of subjects in the ivermectin intention to treat group were compared with that observed in inhabitants of the same province during the same period not participating in the program.ResultsFrom 21,232 subjects with COVID-19, 3,266 were offered and agreed to participate in the ivermectin program and 17,966 did not and were considered as controls. A total of 567 participants reported 819 adverse events (AEs); 3.13% discontinued ivermectin due to adverse events. ICU admission was significantly lower in the ivermectin group compared to controls among participants ≥40 year-old (1.2 vs. 2.0%, odds ratio 0.608; p = 0.024). Similarly, mortality was lower in the ivermectin group in the full group analysis (1.5 vs. 2.1%, odds ratio 0.720; p = 0.029), as well as in subjects ≥ 40 year- old (2.7 vs. 4.1%, odds ratio 0.655; p = 0.005).ConclusionsThis report highlights the safety and possible efficacy of high dose ivermectin as a potentially useful intervention deserving public health-based consideration for COVID-19 patients.

RETRACTED: Microbiome-Based Hypothesis on Ivermectin’s Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity

“…Over 40 peer-reviewed studies ( Table 1 ) have demonstrated studies on the effectiveness of IVM in SARS-CoV-2 infection ( Alam et al, 2020 ; Khan et al, 2020 ; Kishoria et al, 2020 ; Reaz et al, 2020 ; Abd-Elsalam et al, 2021 ; Ahmed et al, 2021 ; Ahsan et al, 2021 ; Aref et al, 2021 ; Behera et al, 2021 ; Cadegiani et al, 2021 ; Chaccour et al, 2021 ; Chahla et al, 2021 ; Chowdhury et al, 2021 ; Elalfy et al, 2021 ; Faisal et al, 2021 ; Ferreira et al, 2021 ; Hellwig and Maia, 2021 ; Krolewiecki et al, 2021 ; Lima-Morales et al, 2021 ; López-Medina et al, 2021 ; Mohan et al, 2021 ; Morgenstern et al, 2021 ; Mukarram, 2021 ; Okumuş et al, 2021 ; Podder et al, 2021 ; Rajter et al, 2021 ; Ravikirti et al, 2021 ; Rezk et al, 2021 ; Seet et al, 2021 ; Shahbaznejad et al, 2021 ; Shoumann et al, 2021 ; Abbas et al, 2022 ; Ascencio-Montiel et al, 2022 ; Babalola et al, 2022 ; Beltran Gonzalez et al, 2022 ; Buonfrate et al, 2022 ; Hazan et al, 2022a ; Kerr et al, 2022 ; Lim et al, 2022 ; Mayer et al, 2022 ; Mustafa et al, 2022 ; Ozer et al, 2022 ; Reis et al, 2022 ; Shimizu et al, 2022 ; Zubair et al, 2022 ), with over 80% of studies showing positive outcomes with IVM treatment. Overall, IVM has shown 60–85% improvement in outcomes, including mortality, ventilation, recovery, clearance, and hospital/ICU admissions.…”

“…Overall, IVM has shown 60–85% improvement in outcomes, including mortality, ventilation, recovery, clearance, and hospital/ICU admissions. The effectiveness could be particularly strong at high doses ( Krolewiecki et al, 2021 ; Buonfrate et al, 2022 ; Mayer et al, 2022 ) and for severe SARS-CoV-2 infection ( Beltran Gonzalez et al, 2022 ; Hazan et al, 2022a ; Zubair et al, 2022 ), and one must consider that the effective dose is very affected by food co-administration ( Food and Drug Administration, 2022 ). Thus, there is a tremendous need to ascertain, not whether but how IVM is ideally applied for SARS-CoV-2 infection.…”

Randomized trials - Ivermectin repurposing for COVID-19 treatment of outpatients with mild disease in primary health care centers

“…2020; Krolewiecki, et al, 2020;Elgazzar, et al, 2020). As well as mentioned by Mayer, et al, 2022, "MEURI interventions are applied when there are no treatments of proven efficacy, it is not possible to start clinical trials immediately, existing preliminary data support the intervention, the relevant regulatory, ethical and scientific authorities approve such use, resources are available to minimize risks and Informed consent is obtained from the patient". In Argentina's health system, the emergency of COVID-19 requires the urgent development of strategies to avoid the impact of the disease on our population, prevent the saturation of the health system and allow us to carry out adequate treatments to reduce the mortality of the disease.…”

“…In view of this situation, the Ministry of Health of the Province considered a MEURI Program as a resource to attempt the monitored and controlled use of a treatment not approved for this indication but with preliminary results of adequate safety and potential efficacy. A recent work carried out by the Ministry of Health of La Pampa, Argentina (Mayer, et al, 2022) on a MEURI Program of high-dose Ivermectin in COVID-19 patients highlights the safety and possible efficacy of this drug for the management of COVID-19 patients.…”