Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients

Abstract

Background and objectives An effective treatment option is not yet available for SARS-CoV2, which causes the COVID-19 pandemic and whose effects are felt more and more every day. Ivermectin is among the drugs whose effectiveness in treatment has been investigated. In this study; it was aimed to investigate the presence of gene mutations that alter ivermectin metabolism and cause toxic effects in patients with severe COVID-19 pneumonia, and to evaluate the effectiveness and safety of ivermectin use in the treatment of patients without mutation. Materials and methods Patients with severe COVID19 pneumonia were included in the study, which was planned as a prospective, randomized, controlled, single-blind phase 3 study. Two groups, the study group and the control group, took part in the study. Ivermectin 200 mcg/kg/day for 5 days in the form of a solution prepared for enteral use added to the reference treatment protocol -hydroxychloroquine + favipiravir + azithromycin- of patients included in the study group. Patients in the control group were given only reference treatment with 3 other drugs without ivermectin. The presence of mutations was investigated by performing sequence analysis in the mdr1/abcab1 gene with the Sanger method in patients included in the study group according to randomization. Patients with mutations were excluded from the study and ivermectin treatment was not continued. Patients were followed for 5 days after treatment. At the end of the treatment and follow-up period, clinical response and changes in laboratory parameters were evaluated. Results A total of 66 patients, 36 in the study group and 30 in the control group were included in the study. Mutations affecting ivermectin metabolism was detected in genetic tests of six (16.7%) patients in the study group and they were excluded from the study. At the end of the 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and was 53.3% (16/30) in the control group (p = 0.10). At the end of the study, mortality developed in 6 patients (20%) in the study group and in 9 (30%) patients in the control group (p = 0.37). At the end of the follow-up period, the average peripheral capillary oxygen saturation (SpO2) values of the study and control groups were found to be 93.5 and 93.0%, respectively. Partial pressure of oxygen (PaO2)/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. While the blood lymphocyte count was higher in the study group compared to the control group (1698 ± 1438 and 1256 ± 710, respectively) at the end of the follow-up period (p = 0.24); reduction in serum C-reactive protein (CRP), ferritin and D-dimer levels was more pronounced in the study group (p = 0.02, p = 0.005 and p = 0.03, respectively). Conclusions According to the findings obtained, ivermectin can provide an increase in clinical recovery, improvement in prognostic laboratory parameters and a decrease in mortality rates even when used in patients with severe COVID-19. Consequently, ivermectin should be considered as an alternative drug that can be used in the treatment of COVID-19 disease or as an additional option to existing protocols.

The effects of hyperbaric oxygen therapy (HBOT) on coronavirus disease-2019 (COVID-19): a systematic review

“…COVID-19 is an acute respiratory infection caused by the SARS-CoV-2; it emerged as a novel human pathogen in China at the end of 2019 continues to be a pandemic worldwide [ 1 – 4 ]. The most common manifestations are pneumonia, high fever, myalgia, dry cough, and chest pain [ 5 – 9 ].…”

Evaluation of Ivermectin as a Potential Treatment for Mild to Moderate COVID-19: A Double-Blind Randomized Placebo Controlled Trial in Eastern India

“…Considering use of ivermectin in treatment of COVID-19 patients, several randomised controlled trials (RCTs) documented its beneficial role either as an additional monotherapy or in combination with doxycycline irrespective of severity of the disease (13)(14)(15). COVID-19 patients treated with ivermectin reported to have decreased duration of symptoms, days to COVID negativity (DTN), lower viral load, mortality rate and higher SPO2%, platelet count and improvement of other prognostic laboratory parameters (13)(14)(15)(16)(17). A metanalysis (18) and several prior observational studies (19)(20)(21) have also documented similar observations.…”

“…Despite availability of mainly speculative literature on beneficial role of ivermectin, no prior such data available in an Indian context. Moreover, most prior RCTs either used a 5-day oral regimen (13,14) or a parenteral regimen (17) of ivermectin. Other RCTs used either a single oral dose of ivermectin alone (16) or in combination with doxycycline (15).…”

Anti-viral treatment for SARS-CoV-2 infection: A race against time amidst the ongoing pandemic

“…In a recently published single-center placebo-controlled randomized trial conducted among individuals with mild disease, a 5-day ivermectin course showed no substantial benefits on symptom duration compared with placebo [ 28 ]. In another randomized, single blind study in a population of severely ill COVID-19 patients, the addition of ivermectin for 5 days on a 3-agent treatment protocol consisting of hydroxychloroquine, favipiravir and azithromycin had a diminishing effect on CRP, D-dimer and ferritin levels after an additional 5 day period without significantly affecting mortality, the rate of clinical improvement or oxygenation indices [ 29 ]. Citing a current lack of concrete evidence to point towards a clear benefit of ivermectin for SARS-CoV-2 infection, both the EMA and the WHO have advised against its use outside the context of clinical trials for the time being.…”