Abstract: [ 266 Asian Pacific Journal of Tropical Medicine 2021; 14(6): 266-273 apjtm.org Original Article Asian Pacific Journal of Tropical Medicine doi: 10.4103/1995-7645.318304 Impact Factor: 1.94 Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial Morteza Shakhsi Niaee1, Peyman Namdar2, Abbas Allami3, Leila Zolghadr4, Amir Javadi5, Amin Karampour3, Mehran Varnaseri6, Behzad Bijani7, Fatemeh Cheraghi1, Yazdan Naderi8, Fatemeh Amini9, Masoumeh Karamyan6,  Mohammad Jafar YadYad6, Ramin Jamshidian6, Nematollah Gheibi8 Sciences and Technology Park, Qazvin, Iran 1 Department of Surgery, Qazvin University of Medical Sciences, Qazvin, Iran 2 Department of Infectious Diseases, Clinical Research Development Unit, BouAliSina Hospital, Qazvin University of Medical Sciences, Qazvin, Iran 3 Department of Chemistry, Imam Khomeini International University Qazvin, Iran 4 Department of Social Sciences School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran 5 Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 6 Department of Infectious Diseases, Qazvin University of Medical Sciences, Qazvin, Iran 7 Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran 8 Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 9 ABSTRACT Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences. Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin (200 µg/kg), three low interval doses of ivermectin (200, 200, 200 µg/kg), single dose ivermectin (400 µg/kg), and three high interval doses of ivermectin (400, 200, 200 µg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7% (5/30) and 20.0% (6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parameters shows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19. KEYWORDS: SARS-COV-2; Ivermectin; Randomized controlled trial; Dose-respond relationship