Clinical study evaluating the efficacy of ivermectin in COVID‐19 treatment: A randomized controlled study

Abstract

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID‐19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID‐19 infected patients. This was a randomized open‐label controlled study that included 164 patients with COVID‐19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant ( p = 0.085). Three patients (3.7%) in each group required mechanical ventilation ( p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups ( p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin‐treated group.

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

“…Overall, 115 studies with 77,128 patients reported the number of patients requiring mechanical ventilation during the study period. We included ACEIs/ARBs, ammonium chloride, azithromycin, bamlanivimab, baricitinib plus remdesivir, bromhexine, budesonide, camostat mesilate, canakinumab, chloroquine, colchicine, convalescent plasma, dexamethasone, doxycycline, favipiravir, hydroxychloroquine, hydroxychloroquine plus azithromycin, hydroxychloroquine plus favipiravir, imatinib, INM005, interferon beta, intravenous immunoglobulin, ivermectin, lopinavir/ritonavir, methylprednisolone, recombinant human GCSF, remdesivir, sarilumab, sofosbuvir plus daclatasvir, sulodexide, tocilizumab, tofacitinib, vitamin D3 and SOC as treatment nodes in the NMA, for which observations came from 84 studies ( 3 , 6 , 22 – 26 , 28 – 31 , 35 , 42 , 43 , 46 , 47 , 50 , 53 , 55 , 57 – 61 , 63 , 64 , 66 , 67 , 71 , 73 – 77 , 79 , 80 , 82 , 83 , 85 – 87 , 89 , 92 – 94 , 96 – 100 , 102 , 105 – 107 , 109 , 111 – 118 , 120 – 124 , 126 , 128 – 132 , 134 , 135 , 139 , 140 , 145 , 151 , 152 , 154 – 156 ). About one-third (26/84) of the included studies were evaluated as low risk ( Supplementary Table 6 ).…”

ESCMID COVID-19 living guidelines: drug treatment and clinical management

“… Ivermectin vs Standard care People: Adult patients with COVID-19 Setting: Inpatients (10 studies), Outpatients (7 studies) Intervention: Ivermectin Comparison: Standard Care (15 studies), HCQ (1 study), Lopinavir/ritonavir (1 study) Outcomes Absolute Effect Relative effect (95% CI) Number of studies Certainty of the evidence (GRADE) Without Ivermectin (Standard Care) With Ivermectin All-cause mortality Within 28 days of commencing treatment 53 per 1000 22 per 1000 RR 0.41 (0.19 to 0.92) 6 [ 17 , 45 , 47 , [117] , [118] , [119] ] (1079 patients) ⊕⊕⊖⊖ Low (serious risk of bias and serious imprecision Difference: 31 fewer per 1000 (95% CI: 43 fewer to 4 more) Mechanical ventilation Within 28 days of commencing treatment 40 per 1000 30 per 1000 RR 0.75 (0.23 to 2.43) 4 [ 88 , 117 , 118 ] (497 patients) ⊕⊕⊖⊖ Low (very serious imprecsion) Difference: 4 fewer per 1000 (95% CI: 31 fewer to 57 more) Serious adverse events End of treatment 7 per 1000 8 per 1000 RR 1.12 (0.21 to 5.88) 6 [ [42] , [43] , [44] , 47 , 120 , 121 ] (644 patients) ⊕⊕⊖⊖ Low (Very Serious imprecision, ) ...…”

“… 95% CI: 95% Confidence interval; RR: Risk ratio. References: [ 17 , 39 , 40 , [42] , [43] , [44] , [45] , [46] , [47] , [117] , [118] , [119] , [120] , [121] , [122] , [123] ]. Evidence adopted Australian guidelines for the clinical care of people with COVID-19, Available at: https://app.magicapp.org/#/guideline/5446/section/78706 .…”

“… References: [ 17 , 39 , 40 , [42] , [43] , [44] , [45] , [46] , [47] , [117] , [118] , [119] , [120] , [121] , [122] , [123] ]. …”

Characteristics of published/registered clinical trials on COVID-19 treatment: A systematic review

“…Multiple RCTs have studied ivermectin use in COVID-19 patients. Some RCTs could not found any clinical efficacy of ivermectin [63][64][65], while others have reported faster time to recovery of COVID-19 disease [66][67][68][69][70], a remarkable decrease of cytokines and inflammatory markers [67,68], faster viral clearance [71], or decrease in mortality rate [67,68] in participants who received ivermectin in comparison with the standard treatment protocol. Nevertheless, the majority of these RCTs had methodological issues like small sample sizes, various ivermectin dosages, and different concomitant drugs given to the patients.…”