Hydroxychloroquine in patients mainly with mild to moderate COVID–19: an open–label, randomized, controlled trial

Abstract

Objectives To assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19.Design Multicenter, open-label, randomized controlled trial.Setting 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020.Participants 150 patients hospitalized with COVID-19. 75 patients were assigned to HCQ plus SOC and 75 were assigned to SOC alone (control group).Interventions HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary endpoint was the 28-day negative conversion rate of SARS-CoV-2. The assessed secondary endpoints were negative conversion rate at day 4, 7, 10, 14 or 21, the improvement rate of clinical symptoms within 28-day, normalization of C-reactive protein and blood lymphocyte count within 28-day. Primary and secondary analysis was by intention to treat. Adverse events were assessed in the safety population. ResultsThe overall 28-day negative conversion rate was not different between SOC plus HCQ and SOC group (Kaplan-Meier estimates 85.4% versus 81.3%, P=0.341). Negative conversion rate at day 4, 7, 10, 14 or 21 was also similar between the two groups. No different 28-day symptoms alleviation rate was observed between the two groups. A significant efficacy of HCQ on alleviating symptoms was observed when the confounding effects of anti-viral agents were removed in the post-hoc analysis (Hazard ratio, 8.83, 95%CI, 1.09 to 71.3). This was further supported by a significantly greater reduction of CRP (6.986 in SOC plus HCQ versus 2.723 in SOC,

Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19

“…Notably, results from an open-label, randomised, controlled trial using doses as high as HCQ 1200 mg for 3 days (followed by a maintenance dose of 800 mg daily for 2-3 weeks) did not suggest efficacy of HCQ in suppressing viral replication. 22 These efficacy data, and the irrefutable clinical data collected through the COVID-19 Global Rheumatology Alliance registry, establish that patients with lupus on baseline therapy with HCQ are not universally protected from COVID-19.…”

COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions

“…One such randomized trial, DISCOVERY, has been launched in Europe and will compare the effectiveness of hydroxychloroquine plus standard of care versus standard of care alone and, in other arms of the study, the effectiveness of remdesivir, lopinavir plus ritonavir, and lopinavir plus ritonavir plus interferon beta (39). Interestingly, the results from a multicenter, open-label randomized trial of 150 patients in China treated with hydroxychloroquine versus SOC for 28 days did not demonstrate relief of symptoms and the hydroxychloroquine group reported significantly higher levels of side effects (30% versus 8.8%) (40). Treatment with hydroxychloroquine did, however, lower C-reactive protein (CRP) levels, thus supporting an anti-inflammatory action of the drug.…”

Emergency Authorization of Chloroquine and Hydroxychloroquine for Treatment of COVID-19

“…Touret and de Lamballerie 15 CQ inhibits the replication of SARS-CoV in Vero E6 cells CQ can be highly effective against HCoV-OC43 infection in newborn mice Wang et al 16 CQ effective in vitro against isolates of 2019-nCOV Yao et al 17 HCQ is more potent than CQ against SARS-CoV-2 in vitro Gao et al 18 CQ effective at improving pneumonia exacerbation, findings on lung imaging, promoting virusnegative conversion, and shortening COVID-19 without serious adverse reactions Gautret et al 19 HCQ treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients, and its effect is reinforced by azithromycin Lover 21 Reanalysis of Gautret et al 19 data shows HCQ monotherapy had modest to no impact on clearance of viremia, but HCQ + AZT showed more significant results Molina et al 22 HCQ + AZT showed no evidence of rapid antiviral clearance or clinical benefit in severe COVID-19 Tang et al 23 HCQ did not result in a higher negative conversion rate but more alleviation of clinical symptoms than SOC alone in patients hospitalized with COVID-19 without receiving antiviral treatment Chen et al 24 HCQ a baseline echocardiogram as well as liver and renal function. Noteworthy drug interactions include increased hypoglycemic risk with antidiabetic medications or insulin, increased risk of ventricular arrhythmia with arrhythmogenic drugs, and impaired efficacy of antiepileptic drugs.…”