Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial

Abstract

Background: We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 (COVID-19).

Methods: An open-label parallel randomized controlled trial was performed among healthy migrant workers quarantined in a large multi-storey dormitory in Singapore. Forty clusters (each defined as individual floors of the dormitory) were randomly assigned to receive a 42-day prophylaxis regimen of either oral hydroxychloroquine (400 mg once, followed by 200 mg/day), oral ivermectin (12 mg once), povidone-iodine throat spray (3 times/day, 270 μg/day), oral zinc (80 mg/day)/vitamin C (500 mg/day) combination, or oral vitamin C, 500 mg/day. The primary outcome was laboratory evidence of SARS-CoV-2 infection as shown by either: (1) a positive serologic test for SARS-CoV-2 antibody on day 42, or (2) a positive PCR test for SARS-CoV-2 at any time between baseline and day 42.

Results: A total of 3037 asymptomatic participants (mean age, 33.0 years; all men) who were seronegative to SARS-CoV-2 at baseline were included in the primary analysis. Follow-up was nearly complete (99.6%). Compared with vitamin C, significant absolute risk reductions (%, 98.75% confidence interval) were observed for oral hydroxychloroquine (21%, 2-42%) and povidone-iodine throat spray (24%, 7-39%). No statistically significant differences were observed with oral zinc/vitamin C combination (23%, -5 to +41%) and ivermectin (5%, -10 to +22%). Interruptions due to side effects were highest among participants who received zinc/vitamin C combination (6.9%), followed by vitamin C (4.7%), povidone-iodine (2.0%), and hydroxychloroquine (0.7%).

Conclusions: Chemoprophylaxis with either oral hydroxychloroquine or povidone-iodine throat spray was superior to oral vitamin C in reducing SARS-CoV-2 infection in young and healthy men.

Keywords: Hydroxychloroquine; Ivermectin; Povidone-iodine; SARS-CoV-2; Vitamin C; Zinc.

Fig. 1

Screening and randomization. Of the 5255 individuals assessed for eligibility, 998 did not meet the eligibility criteria at the time of screening and were excluded. A further 849 individuals who met the eligibility criteria were excluded as they were recruited from non-randomized floors; participants from hydroxychloroquine and ivermectin assigned floors who met additional study exclusions and received vitamin C formed part of the 849 excluded individuals. Overall, 40 clusters were randomized in equal ratios to receive the different interventions, involving 3408 men. In the hydroxychloroquine arm, 48 were excluded due to baseline seropositivity, and one withdrew from the study; data from the remaining 432 participants who received hydroxychloroquine were included in the primary analysis. In the ivermectin arm, 88 were excluded due to baseline seropositivity, and four participants withdrew from the study; the remaining 617 participants were included in the primary analysis for ivermectin. Of the 863 randomized participants in the povidone-iodine arm, 125 were excluded due to baseline seropositivity; three participants withdrew from the study; the remaining 735 participants were included in the primary analysis for povidone-iodine. In the zinc/vitamin C arm, of the 692 randomized participants, 56 were excluded due to baseline seropositivity, and two participants withdrew from the study; the remaining 634 participants were included in the primary analysis for zinc/vitamin C. In the vitamin C arm, of the 663 randomized participants, 42 were excluded due to baseline seropositivity, and two participants withdrew from the study; the remaining 619 participants were included in the primary analysis for vitamin C.