Bromhexine for Post-exposure COVID-19 Prophylaxis: A Randomized, Double-blind, Placebo-controlled Trial

Background: Limited medications are available for post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) infection. Whether bromhexine can prevent or mitigate symptomatic infection after virus exposure is undetermined. Objectives: We aimed to evaluate bromhexine's effect on preventing COVID-19 after close contact exposure. Methods: A multi-center randomized, double-blind, placebo-controlled clinical trial was conducted on 372 adults (>= 18 years) who had close contact within four days with a household member with confirmed COVID-19. They were randomly assigned to receive bromhexine 8 mg (n = 187) or placebo (n = 185) three times a day for two weeks. The primary outcome was the incidence of symptomatic COVID-19. Secondary outcomes included hospitalization or death, confirmed COVID-19 by Polymerase Chain Reaction (PCR) in symptomatic patients, and adverse drug reactions. Results: The incidence of symptomatic COVID-19 was significantly lower in individuals who received bromhexine than in those who received the placebo (16 [8.6%] vs. 34 [18.4%], relative risk = 0.47, P = 0.005). PCR confirmation was reported in 13 (7.0%) and 26 (14.1%) individuals in the bromhexine and placebo groups, respectively (P = 0.025), with a relative risk reduction of 50%. The hospitalization rate, death, and medication side effects did not vary significantly between the bromhexine and placebo arms. Conclusions: Bromhexine is an effective, non-invasive, affordable agent with a low side-effect profile to prevent symptomatic COVID-19. Early use of bromhexine potentially provides another layer of protection; hence, it can play a role in controlling the pandemic.