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Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial
15 Pages Posted: 20 Dec 2021More...
Background: Limited number of medications are available for the post-exposure prophylaxis of COVID-19 infection. Whether bromhexine can prevent or mitigate symptomatic infection after virus exposure is undetermined.
Methods: A multi-center randomized; double-blind, placebo-controlled clinical trial was conducted. The 372 adults (≥18 years) who had close contact within 4 days with a household member with confirmed COVID-19 were randomly assigned to receive bromhexine (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 the incidence of hospitalization or death, the incidence of confirmed COVID-19 detection by PCR in symptomatic patients and presence of adverse drug reactions.
Findings: 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%) of the 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 or placebo arms.
Interpretation: Bromhexine is an effective, non-invasive, and affordable agent with a low side-effect profile to prevent symptomatic COVID-19. Early use of bromhexine potentially provides another layer of protection and hence it can play a prominent role in ending the pandemic especially given the emergence of new variants and the vaccination challenges faced by developing countries.
Trial Registration: The trial was registered with the Iranian Registry of Clinical
Trials (https://www.irct.ir/), a primary registry in the World Health Organization network, registration code IRCT20120703010178N22.
Funding: Primary funding sourceOffice of Deputy of Research and Technology, SBUMS, Tehran, Iran.
Declaration of Interest: Nothing to report except Dr. Ramin Tolouian received speaker honorarium from Sanofi-Genzyme and consulting fee from Travere therapeutics.
Ethical Approval: The trial was conducted from December 21, 2020, to July 25, 2021, in four medical centers, in Tehran, Iran. The
trial was approved by the ethics committee review board at the Shahid Beheshti University of Medical Sciences with
the code of IR.SBMU.PHARMACY.REC.1399.247.
Keywords: COVID-19, Bromhexine, Post exposure, Prophylaxis, Symptomatic disease, Clinical trial, TMPRSS2
Suggested Citation: Suggested Citation