Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19

Abstract

Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. Methods We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. Results A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P=1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P=1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. Conclusions Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123 .)

Drug treatments for covid-19: living systematic review and network meta-analysis

“…Hydroxychloroquine might increase the risk of adverse events leading to drug discontinuation compared with the other interventions. Notably, this iteration of the living network meta-analysis did not include four recently published randomised controlled trials on hydroxychloroquine compared with standard care 66676873. RECOVERY, the largest randomised controlled trial on hydroxychloroquine, suggests that hydroxychloroquine might not reduce mortality and might increase length of hospital stay 66.…”

The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients

“…One of them also reported no benefit in need for admissions or clinical improvement [37]. The lack of clinical improvement was reported in another trial [38]. Finally, two more RCTs have reported no association between HCQ and virological clearance [39] or prevention of disease in individuals exposed to it [40].…”

The therapeutic effect and safety of the drugs for COVID-19: a systematic review and meta-analysis

“…In early February, chloroquine/hydroxychloroquine was reported to have apparent antiviral effect on SARS-CoV-2 11 , and then it was recommend for treatment of COVID-19 patients soon. As the clinical trials continued, chloroquine/hydroxychloroquine didn't exert the clinical effect as people expected 36,37 , thus it was gradually not recommended for use alone. We comprehensively analyzed data of the trials which used chloroquine/hydroxychloroquine and con rmed it did not reduce the mortality signi cantly as compared with standard care.…”

“…The screening process was shown in figure 1 and 3860 studies were identified according to the research strategy initially. In total, 22 studies containing 12795 patients were adopted in our study and all of them were published in English 10,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] . Among trails included, half of them were RCTs, and the other were Non-RCTs.…”