Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

Abstract

Background: It appears that ivermectin can potentially act against COVID-19 infection. Today, it is an urgent need to evaluate the efficacy and safety of ivermectin. The effect of ivermectin therapy on mild to severe COVID-19 patients was investigated.Methods: A 45-days randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial was designed at five hospitals. A total number of 180 mild to severe hospitalized patients with confirmed PCR and chest image tests were enrolled. The radiographic findings, hospitalization and low O2 saturation duration, and clinical outcomes such as mortality and variables of blood samples were analyzed using standard statistical analyses in SPSS (V20).Results: Average age of the participants was 56 years (45-67) and 50% were women. The primary and secondary results showed significant changes between day zero and day five of admission (∆ 0/5) in terms of ΔALC5/0, ΔPLT5/0, ΔESR5/0, ΔCRP5/0, duration of low O2 saturation, and duration of hospitalization (CI = 95% ). Risk of mortality was also decreased significantly in the study groups.Conclusion: Ivermectin as an adjunct reduced the rate of mortality, low O2 duration, and duration of hospitalization in adult COVID 19 patients. The improvement of other clinical parameters showed that the ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.Trial Registration: This trial was registered with the Iranian Registry of Clinical Trials website (registration ID IRCT20200408046987N1).

The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis

“…After screening, six randomized controlled trials [5][6][7][8][9][10] were included with a total of 658 patients who were randomized to receive ivermectin, and 597 patients were randomized to the control group who did not receive ivermectin. The six randomized trials that were included in the meta-analysis were respectively from Iraq [5], Iran [6], Bangladesh [7], Egypt [8], Turkey [9], and India [10]. Details of the included studies are shown in Table 1.…”

“…The overall risk of bias assessed by RoB 2 is presented in Table 1. The trial by Niaee et al [6] and Ravikirti et al [10] had an overall low risk of bias. The other trials had an overall high risk of bias; the trial led by Mahmud et al [7] had a high risk of bias in the domain of missing outcome data since a significant proportion (21%) of participants randomized was not included in the analysis; the trial by Elgazzar et al [8] had a high risk of bias in the domain of randomization since the protocol for randomization was not reported; the trial by Hashim et al [5] had a high risk of bias in the domain of randomization due to simple randomization method used with no information on allocation concealment and had also some concerns of bias in the domain of deviations from intervention due to unblinded participants; the trial led by Okumuş et al [9] had a high risk of bias in the domain of randomization due to simple randomization method used and had also a high risk of bias in the domain of deviations from intended interventions due to open-label nature of the trial.…”

“…Some may be concerned by the absence of real-time reverse transcription-polymerase chain reaction confirmatory test for COVID-19 diagnosis in a significant fraction of subjects in the trial by Niaee et al [6], but exclusion of this trial in the meta-analysis still observed a significantly reduced risk of mortality with the use of ivermectin among patients with COVID-19 relative to non-use of ivermectin (pooled odds ratio = 0.23; 95% confidence interval 0.09-0.56).…”

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19

“…To our knowledge, preliminary reports of other randomized trials of ivermectin as treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals. [28][29][30][31] Daily doses were used in this trial because pharmacokinetic models have shown higher lung concentrations with daily rather than intermittent dosing, 32 and have proven to be well tolerated. 33,34 In addition, the US Food and Drug Administration-approved dose for the treatment of helminthic diseases (200 μg/kg) showed clinical benefit in an observational study, 27 supporting a hypothesis that higher doses could be clinically relevant.…”

Ivermectin in the treatment of COVID-19- friend or foe?

“…At least eight of these seem to have been completed to date, and the forthcoming publication of the relevant study results is being eagerly anticipated. [43][44][45][46][47][48][49][50][51][52][53][54][55][56]58…”