ObjectivesThe established effect of cetylpyridinium chloride (CPC) mouthwash on SARS-CoV-2 viral titers is unclear. No clinical trial has examined the impact of on-demand aqueous chlorine dioxide mouthwash on SARS-CoV-2 viral titer. MethodsIn this multicenter, three-armed, randomized, open-label, placebo-controlled clinical trial involving mildly symptomatic COVID-19 patients, we randomly assigned them to receive 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of purified water as a placebo mouthwash in a 1:1:1 ratio. The primary measurement was the SARS-CoV-2 viral titer in saliva, evaluated by a mixed-effects linear regression model. Results49 patients received CPC mouthwash (n=16), on-demand aqueous chlorine dioxide mouthwash (n=16), and placebo (n=17) between January 14, 2024, and February 20, 2024. 0.05% CPC mouthwash significantly reduced salivary viral titer at 10 minutes post-use (-0.97 log10 PFU/mL; 95% CI, -1.64 to -0.30; P=0.004), while no such effect was observed at 30 minutes (difference vs. placebo, -0.26 log10 PFU/mL; 95% CI, -0.92 to 0.40; P=0.435) or 60 minutes (difference vs. placebo, -0.05 log10 PFU/mL; 95% CI, -0.68 to 0.58; P=0.877). 0.01% on-demand chlorine dioxide mouthwash did not reduce salivary viral titer at 10 min, 30 min, or 60 min compared to placebo. Conclusions10 minutes after using a 0.05% CPC mouthwash, the salivary viral titer of SARS-CoV-2 decreased compared to placebo. 0.01% on-demand aqueous chlorine dioxide mouthwash and placebo had no significant difference in SARS-CoV-2 viral titers. Trial RegistrationJapan Registry of Clinical Trials (jRCT): jRCTs031230566.
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