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0 0.5 1 1.5 2+ Hospitalization 80% Improvement Relative Risk Symp. case 91% Case 71% primary Bromhexine  Mikhaylov et al.  Prophylaxis  RCT Is prophylaxis with bromhexine beneficial for COVID-19? RCT 50 patients in Russia (May - July 2020) Lower hospitalization (p=0.49) and fewer symptomatic cases (p=0.05), not sig. Mikhaylov et al., Interdisciplinary Pe.., Mar 2021 Favors bromhexine Favors control

Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study

Mikhaylov et al., Interdisciplinary Perspectives on Infectious Diseases, doi:10.1155/2022/4693121 (date from preprint), NCT04405999
Mar 2021  
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Small prophylaxis RCT with 25 treatment and 25 control health care workers, showing lower PCR+, symptomatic cases, and hospitalization with treatment, although not statistically significant with the small sample size.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants Peacock, Willett.
risk of hospitalization, 80.0% lower, RR 0.20, p = 0.49, treatment 0 of 25 (0.0%), control 2 of 25 (8.0%), NNT 12, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of symptomatic case, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), NNT 5.0, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of case, 71.4% lower, RR 0.29, p = 0.14, treatment 2 of 25 (8.0%), control 7 of 25 (28.0%), NNT 5.0, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mikhaylov et al., 8 Mar 2021, Randomized Controlled Trial, Russia, peer-reviewed, 8 authors, study period 13 May, 2020 - 25 July, 2020, trial NCT04405999 (history). Contact:
This PaperBromhexineAll
Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study
MD, PhD Evgeny N Mikhaylov, MD, PhD Tamara A Lyubimtseva, MD Aleksandr D Vakhrushev, MD, DESA Dmitry Stepanov, MD, PhD Dmitry S Lebedev, MD Elena Yu Vasilieva, MD, PhD Alexandra O Konradi, MD, PhD Evgeny V Shlyakhto
Background: Bromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection. Methods : In a single-center randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollμent of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included: time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; adverse events. Results: The rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs 5/25; P = 0.02). Conclusion: Although the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or NCT04405999
AUTHOR CONTRIBUTIONS . Control group Overall
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