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

Galan, Luis Enrique Bermejo; dos Santos, Nayara Melo; Asato, Mauro Shosuka; Araújo, Jucineide Vieira; de Lima Moreira, Adriana; Araújo, Aléxia Mahara Marques; Paiva, Artur Diogenes Pinheiro; Portella, Diego Guilherme Santos; Marques, Frank Silas Saldanha; Silva, Gabriel Melo Alexandre; de Sousa Resende, Joana; Tizolim, Marycassiely Rodrigues; Santos, Poliana Lucenados; Buttenbender, Steffi Ferreira; de Andrade, Stephanye Batista; Carbonell, Roberto Carlos Cruz; Da Rocha, Juliana Gomes; de Souza, Ruy Guilherme Silveira; da Fonseca, Allex Jardim

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.