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All Studies   Meta Analysis    Recent:   

Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial

Tolouian et al., SSRN, doi:10.2139/ssrn.3989
Dec 2021  
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Mortality 33% Improvement Relative Risk Hospitalization 70% Symp. case 53% Case 50% Bromhexine  Tolouian et al.  Prophylaxis  DB RCT Is prophylaxis with bromhexine beneficial for COVID-19? Double-blind RCT 372 patients in Iran (December 2020 - July 2021) Fewer symptomatic cases (p=0.007) and cases (p=0.028) Tolouian et al., SSRN, December 2021 Favorsbromhexine Favorscontrol 0 0.5 1 1.5 2+
PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants1,2.
risk of death, 32.9% lower, RR 0.67, p = 0.76, treatment 0 of 187 (0.0%), control 1 of 185 (0.5%), odds ratio converted to relative risk, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of hospitalization, 70.3% lower, RR 0.30, p = 0.14, treatment 1 of 187 (0.5%), control 6 of 185 (3.2%), adjusted per study, odds ratio converted to relative risk.
risk of symptomatic case, 53.0% lower, RR 0.47, p = 0.007, treatment 16 of 187 (8.6%), control 34 of 185 (18.4%), NNT 10, odds ratio converted to relative risk.
risk of case, 50.2% lower, RR 0.50, p = 0.03, treatment 13 of 187 (7.0%), control 26 of 185 (14.1%), NNT 14, odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Tolouian et al., 20 Dec 2021, Double Blind Randomized Controlled Trial, placebo-controlled, Iran, preprint, 16 authors, study period 21 December, 2020 - 25 July, 2021.
This PaperBromhexineAll
Bromhexine, for post exposure COVID-19 prophylaxis: A Randomized, Double-Blind, Placebo Control Trial
Ramin Tolouian, MD Omid Moradi, Zuber D Pharmd, Mulla, PhD Shadi Ziaie, Mehrdad Pharmd, Haghighi, MD Hadi Esmaily, Hossein Pharmd, Amini, PharmD Rezvan Hassanpour, Elham Pharmd, Pourheidar, Mehran Pharmd, Kouchek, MD Alireza Manafi-Rasi, MD Shahnaz Sali, MD Sara Abolghasemi, MD Shabnam Tehrani, MD Audrey C Tolouian, PharmD Mohammad Sistanizad
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). PCRconfirmation 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.
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