Abstract: Am. J. Trop. Med. Hyg., 103(4), 2020, pp. 1635–1639 doi:10.4269/ajtmh.20-0873 Copyright © 2020 by The American Society of Tropical Medicine and Hygiene Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study Sherief Abd-Elsalam,1* Eslam Saber Esmail,1 Mai Khalaf,1 Ehab Fawzy Abdo,2 Mohammed A. Medhat,2 Mohamed Samir Abd El Ghafar,3 Ossama Ashraf Ahmed,4 Shaimaa Soliman,5 Ghada N. Serangawy,6 and Mohamed Alboraie7 1 Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt; 2Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Anesthesia, Surgical Intensive Care and Pain Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt; 4Department of Internal Medicine, Ain-Shams University, Cairo, Egypt; 5Public Health and Community Medicine, Menoufia University, Menoufia, Egypt; 6Department of Forensic Medicine and Toxicology, Faculty of Medicine, Tanta University, Tanta, Egypt; 7Department of Internal Medicine, Al-Azhar University, Cairo, Egypt Abstract. 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.