Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study
Sherief Abd-Elsalam, Eslam Saber Esmail, Mai Khalaf, Ehab Fawzy Abdo, Mohammed A Medhat, Mohamed Samir Abd El Ghafar, Ossama Ashraf Ahmed, Shaimaa Soliman, Ghada N Serangawy, Mohamed Alboraie
The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0873
The COVID-19 pandemic is showing an exponential growth, mandating an urgent need to develop an effective treatment. Indeed, to date, a well-established therapy is still lacking. We aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) added to standard care in patients with COVID-19. This was a multicenter, randomized controlled trial conducted at three major university hospitals in Egypt. One hundred ninety-four patients with confirmed diagnosis of COVID-19 were included in the study after signing informed consent. They were equally randomized into two arms: 97 patients administrated HCQ plus standard care (HCQ group) and 97 patients administered only standard care as a control arm (control group). The primary endpoints were recovery within 28 days, need for mechanical ventilation, or death. The two groups were matched for age and gender. There was no significant difference between them regarding any of the baseline characteristics or laboratory parameters. Four patients (4.1%) in the HCQ group and 5 (5.2%) patients in the control group needed mechanical ventilation (P = 0.75). The overall mortality did not differ between the two groups, as six patients (6.2%) died in the HCQ group and 5 (5.2%) died in the control group (P = 0.77). Univariate logistic regression analysis showed that HCQ treatment was not significantly associated with decreased mortality in COVID-19 patients. So, adding HCQ to standard care did not add significant benefit, did not decrease the need for ventilation, and did not reduce mortality rates in COVID-19 patients.
References
Abena, Chloroquine and hydroxychloroquine for the prevention or treatment of COVID-19 in Africa: caution for inappropriate off-label use in healthcare settings, Am J Trop Med Hyg
Alexander, Debono, Mammen, Iorio, Aryal et al., COVID-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine, J Clin Epidemiol
Bhandari, Characteristics, treatment outcomes and role of hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur city: an epidemio-clinical study, J Assoc Physicians India
Bhatnagar, Murhekar, Soneja, Gupta, Giri et al., Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: protocol for restricted public health emergency use, Indian J Med Res
Boulware, A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19, N Engl J Med
Cao, A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19, N Engl J Med
Cavalcanti, Hydroxychloroquine with or without azithromycin in mildto-moderate COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2019014Faul, Erdfelder, Lang, Buncher, G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences, Behav Res Methods
Gautret, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label nonrandomized clinical trial, Int J Antimicrob Agents
Geleris, Observational study of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med
Gnegel, Hauk, Neci, Mutombo, Nyaah et al., Identification of falsified chloroquine tablets in Africa at the time of the COVID-19 pandemic, Am J Trop Med Hyg
Lim, Jeon, Shin, Kim, Seong et al., Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR, J Korean Med Sci
Molina, Delaugerre, Goff, Lima, Ponscarme et al., No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection, Med Mal Infect
Sarin, APASL COVID Task Force, APASL COVID Liver Injury Spectrum Study, 2020. Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; the APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study), Hepatol Int
Sarma, Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis, J Med Virol
Skipper, Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial, Ann Intern Med
Tang, Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ
Udwadia, Malu, Rana, Joshi, Hydroxychloroquine for COVID-19: what is our current state of knowledge?, J Assoc Physicians India
Xie, Chen, Insight into 2019 novel coronavirus -an updated interim review and lessons from SARS-CoV and MERS-CoV, Int J Infect Dis
Yin, Wunderink, MERS, SARS and other coronaviruses as causes of pneumonia, Respirology
Zhou, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Zhu, China Novel Coronavirus Investigating and Research Team, 2020. A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med
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'journal-title': 'Infect Disord Drug Targets'}],
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