Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial

Abstract

Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

“…Two trials compared lopinavir–ritonavir added to standard care versus standard care alone [ 33 , 41 ]. Eight trials compared hydroxychloroquine added to standard care versus standard care alone [ 35 , 36 , 43 , 49 , 55 , 56 , 59 , 60 ]. Two trials compared convalescent plasma added to standard care versus standard care alone [ 40 , 52 ].…”

“…We identified 8 trials comparing hydroxychloroquine added to standard care versus standard care alone [ 35 , 36 , 43 , 49 , 55 , 56 , 59 , 60 ]. We also identified one trial that used placebo as an additional control intervention [ 54 ].…”

“…Visual inspection of the forest plot and measures to quantify heterogeneity (I 2 = 0%) indicated no heterogeneity. The assessment time points varied from 5 [ 35 ] to 28 [ 49 , 56 , 59 ] days after randomization. The trial sequential analysis showed that we had enough information to reject that hydroxychloroquine compared with standard care reduces all-cause mortality with a relative risk reduction of 20% ( S6 Fig ).…”

Enantiomers of Chloroquine and Hydroxychloroquine Exhibit Different Activities Against SARS-CoV-2in vitro, EvidencingS-Hydroxychloroquine as a Potentially Superior Drug for COVID-19

“…These include some medications commonly used for decades, such as chloroquine, [11][12][13] arbidol, 14 ribavirin, [15][16][17] lopinavir, etc., [18][19][20] The list also contains some drugs in development, for instance, remdesivir, 11,17 a previously studied drug candidate for treating Ebola infection. [21][22] Among the most notable and also controversial repurposed drugs are chloroquine (CQ) and hydroxychloroquine (HCQ) as shown in Figure 1A, with several initial promising results especially when combined with azithromycin or zinc supplement being reported, [23][24][25][26][27][28][29][30][31] only to be followed by contradicting reports [32][33][34][35][36][37] on lack of efficacy and presence of severe side effects, especially among the higher dosed patients. Based on the preclinical results, both CQ and HCQ have displayed inhibition of viral replication.…”

De Novo Design and Bioactivity Prediction of SARS-CoV-2 Main Protease Inhibitors Using ULMFit

“…The global pandemic of coronavirus disease (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) created a rush to discover drug candidates against the virus [1][2][3] . As of June 2020, no vaccine or molecule has been approved for treatment of COVID-19, despite many molecules being screened and entering clinical trials, including remdesivir, chloroquine and lopinavir [4][5][6] . Therefore, there is an urge to boost drug discovery campaigns in order to identify safe and potent antivirals to tackle the COVID-19 pandemic.…”