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0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ansarin (RCT) 91% 0.09 [0.01-1.59] death 0/39 5/39 Improvement, RR [CI] Treatment Control Li (RCT) 75% 0.25 [0.06-1.00] no disch. 2/12 4/6 Tau​2 = 0.00; I​2 = 0.0% Early treatment 79% 0.21 [0.06-0.72] 2/51 9/45 79% improvement Mareev (RCT) 39% 0.61 [0.14-0.97] no disch. 14/24 20/21 Improvement, RR [CI] Treatment Control Tolouian (RCT) 76% 0.24 [0.01-8.03] death 48 (n) 52 (n) Tau​2 = 0.00; I​2 = 0.0% Late treatment 39% 0.61 [0.43-0.86] 14/72 20/73 39% improvement Mikhaylov (RCT) 80% 0.20 [0.01-3.97] hosp. 0/25 2/25 Improvement, RR [CI] Treatment Control Tau​2 = 0.00; I​2 = 0.0% Prophylaxis 80% 0.20 [0.01-3.97] 0/25 2/25 80% improvement All studies 45% 0.55 [0.40-0.77] 16/148 31/143 45% improvement 5 bromhexine COVID-19 studies Nov 18, 2021 Tau​2 = 0.00; I​2 = 0.0%; Z = 3.46 Effect extraction pre-specified, see appendix Favors bromhexine Favors control
Database of all bromhexine COVID-19 studies. Submit updates/corrections.
Restrict:    All    Early    Late    Prophylaxis
Apr 30
In Silico Sgrignani et al., Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2021.666626 (Peer Reviewed) Computational Identification of a Putative Allosteric Binding Pocket in TMPRSS2
Details   In SIlico study of TMPRSS2 inhibition by camostat, nafamostat, and bromhexine, suggesting allosteric binding for bromhexine, compared to camostat and nafamostat which bind to the active site of TMPRSS2 forming covalent adducts.
Mar 15
Late Tolouian et al., J. Investig. Med., doi:10.1136/jim-2020-001747 (Peer Reviewed)
death, ↓76.0%, p=0.43
Effect of bromhexine in hospitalized patients with COVID-19
Details   Small RCT with 100 patients, 48 with bromhexine added to SOC, showing slower viral- conversion but lower mortality and greater clinical improvement with bromhexine (not statistically significant with few deaths and very high recovery). Th..
Mar 8
PrEPPEP Mikhaylov et al., medRxiv, doi:10.1101/2021.03.03.21252855 (Preprint)
hosp., ↓80.0%, p=0.49
Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study
Details   Small prophylaxis RCT with 25 treatment and 25 control health care worker, showing lower PCR+, symptomatic cases, and hospitalization with treatment, although not statistically significant with the small sample size.
Jan 31
In Vitro Carpinteiro et al., Journal of Biological Chemistry, doi:10.1016/j.jbc.2021.100701 (Peer Reviewed) (In Vitro)
in vitro
Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells
Details   In Vitro study showing that ambroxol (a metabolite of bromhexine) inhibits SARS-CoV-2 infection.
Dec 31
Review Al-Kuraishy et al., Current Medical and Drug Research (Review) (Preprint)
The potential role of Bromhexine in the management of COVID-19: Decipher and a real game-changer
Details   Review article noting that bromhexine is a TMPRSS2 inhibitor with greater effect in lung tissue and attenuates the entry and proliferation of SARS‐CoV‐2.
Dec 3
Late Mareev et al., Кардиология, doi:10.18087/cardio.2020.11.n1440 (Peer Reviewed)
no disch., ↓38.8%, p=0.02
Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
Details   Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone. The odds ratio of having a positive PCR or hospitalization for ≥10 days was 0.07 [0.008–0.61] with treatment. Dosing was bromhexine 8mg 4 times daily, sp..
Sep 3
Early Li et al., Clinical and Translational Science, doi:10.1111/cts.12881 (Peer Reviewed)
no disch., ↓75.0%, p=0.11
Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID‐19: An Open‐Label Randomized Controlled Pilot Study
Details   Tiny RCT with 12 bromhexine and 6 control patients showing non-statistically significant improvements in chest CT, need for oxygen therapy, and discharge rate within 20 days. Authors recommend a larger scale trial.
Jul 19
Early Ansarin et al., Bioimpacts, doi:10.34172/bi.2020.27 (Peer Reviewed)
death, ↓90.9%, p=0.05
Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial
Details   RCT with 39 bromhexine and 39 control patients showing lower mortality, intubation, and ICU admission with treatment. The treatment group received bromhexine hydrochloride 8 mg three times a day for two weeks. All patients received SOC in..
May 26
Theory Depfenhart et al., Internal and Emergency Medicine, doi:10.1007/s11739-020-02383-3 (Peer Reviewed) (Theory)
Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?
Details   Proposal to use bromhexine to inhibit TMPRSS2-specific viral entry for prophylaxis and treatment of COVID-19.
Apr 30
Theory Habtemariam et al., Pharmacol. Res., doi:10.1016/j.phrs.2020.104853 (Peer Reviewed) (Theory)
Possible use of the mucolytic drug, bromhexine hydrochloride, as a prophylactic agent against SARS-CoV-2 infection based on its action on the Transmembrane Serine Protease 2
Details   Note on the potential use of bromhexine hydrochloride for prophylaxis of SARS-CoV-2, based on the role of TMPRSS2 in SARS-CoV-2 infection, and the TMPRSS2 inhibition of bromhexine hydrochloride.
Apr 22
Review Maggio et al., Pharmacol Res., doi:10.1016/j.phrs.2020.104837 (Review) (Peer Reviewed)
Repurposing the mucolytic cough suppressant and TMPRSS2 protease inhibitor bromhexine for the prevention and management of SARS-CoV-2 infection
Details   Proposal to use bromhexine for prophylaxis and treatment of COVID-19 based on TMPRSS2 inhibition, widespread clinical use, and supporting pharmacokinetic and safety data.
Mar 5
In Vitro Hoffman et al., Cell, doi:10.1016/j.cell.2020.02.052 (Peer Reviewed) (In Vitro)
in vitro
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibito
Details   In Vitro study showing that SARS-CoV-2 uses ACE2 for entry and TMPRSS2 for S protein priming, and that TMPRSS2 inhibitor camostat blocked entry and may be an effective treaetment.
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