Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection

Abstract

Objective : Given the urgent need for strategies to minimize the damage caused by this pandemic, this study performed a randomized, double-blind phase 2 study to assess the safety of the effectiveness of chloroquine (CQ), hydroxychloroquine (HCQ) or ivermectin in severe forms of COVID-19, in addition to identifying predictors of mortality in this group of patients. Methods : Phase 2, double-blind, randomized study to assess the safety and efficacy of enteral CQ, HCQ or ivermectin in patients hospitalized for SARS-CoV-2 infection, admitted to a Reference Hospital in Roraima (Brazil) in may 2020. Patients were randomized in a 1:1:1 ratio. The endpoints were need of supplemental O 2 , invasive ventilation, admission in ICU and death. The study was approved by an independent IRB. Results : 168 patients were randomized. The mean age was 53.4 years (±15.6), most participants were male ( n = 95; 58.2%). Therapy with corticosteroid, anticoagulant or antibiotics was a decision of the attending physicians, and there was no difference between the groups. The mortality was similar in three groups (22.2%; 21.3% and 23.0%) suggesting ineffectiveness of the drugs. No difference in the incidence of serious adverse events were observed. To be older than 60 years of age, obesity, diabetes, extensive pulmonary involvement and low SaO 2 at hospital admission due to independent risk factors for mortality. Conclusion : Although CQ, HCQ or ivermectin revealed a favorable safety profile, the tested drugs do not reduce the need for supplemental oxygen, ICU admission, invasive ventilation or death, in patients hospitalized with a severe form of COVID-19.

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

“…However, other risk factors like the patient's age, serum ALT, creatinine, ferritin, and CRP being significantly related to all‐cause mortality may be attributable to the small dose of ivermectin. Accessible pharmacokinetic evidence from clinically significant and excessive dosage trials indicates that the concentration of ivermectin needed to suppress SARS‐CoV‐2 in humans with known dosing regimens is unlikely to be reached in serum and tissue 20–30 . Pott‐Junior et al 24 as well as Babalola et al 25 supported our results that higher doses of ivermectin may have a greater antiviral effect, but also showed that supra‐lethal toxic doses are unnecessary to inhibit viral replication.…”

Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials

“…There were 9 RCTs comprising of 1788 patients included in this systematic review and meta-analysis [ Fig. 1 ] [ [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ]. Baseline characteristics of the included studies can be seen in Table 1 .…”

“…The underlying mechanism for this observation is unclear and requires further investigation. However, this observation might be due to 100% severe COVID-19 in two studies which enroll high percentage of hypertension (Galan et al [ 24 ] and NCT04646109 [ 26 ]), also these studies did not clearly report the presence of coronary artery disease or heart failure, which are important complications of hypertension. Thus, the finding might also be a coincidence or an indicator of other end organ complications.…”

One Year of Coronavirus Disease 2019 (COVID-19) in Brazil: A Political and Social Overview

“…The situation is aggravated by President Jair Messias Bolsonaro's solid support base, which endorses the use of these drugs. After all, the phosphoethanolamine episode in 2016 was a preview of the chloroquine-hydroxychloroquine-ivermectin hype of 2020, which have no proven efficacy in the treatment of COVID-19 and have several adverse effects [83][84][85][86][87][88][89]. However, the backlash was not so high back then as it was in 2020, and the phosphoethanolamine case did not draw the attention of the Brazilian population, in general.…”