Summary of COVID-19 bromhexine studies

50 patient bromhexine prophylaxis RCT: 91% fewer symptomatic cases (p=0.05) and 71% fewer cases (p=0.14).
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.
Mar 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2022/4693121/, https://c19p.org/mikhaylov

2. Vila Méndez et al., Efficacy of Bromhexine versus Standard of Care in Reducing Viral Load in Patients with Mild-to-Moderate COVID-19 Disease Attended in Primary Care: A Randomized Open-Label Trial

191 patient bromhexine early treatment RCT: 67% lower hospitalization (p=0.49) and 7% worse viral clearance (p=0.82).
RCT 191 low risk (no mortality) outpatients in Spain, showing no significant differences with bromhexine. Authors note that "statistical differences between the study groups were observed in the percentage of patients treated with bronchodilators (p = 0.033) and receiving symptomatic treatment (p = 0.034), which were higher in the SOC alone group", but do not provide details or perform adjustments. There were more moderate/severe cases in the treatment group (9 vs. 5). Many results appear to be missing including: reduction in the severity of each symptom (0–10 NRS score) at days 4, 7, 14, and 28 as compared with baseline; proportion of patients with clinical improvement and time to clinical improvement; proportion of patients with disappearance of each symptom at days 4, 7, 14, and 28, and time to disappearance; proportion of asymptomatic patients at days 4, 7, 14, and 28. Bromhexine 48 mg/day for seven days. SOC included acetaminophen.
Dec 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/1/142, https://c19p.org/vilamendez

3. Ansarin et al., Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial

78 patient bromhexine early treatment RCT: 91% lower mortality (p=0.05), 89% lower ventilation (p=0.01), and 82% lower ICU admission (p=0.01).
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 including HCQ.
Jul 2020, Bioimpacts, https://bi.tbzmed.ac.ir/Article/bi-23240, https://c19p.org/ansarin

4. Li et al., Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID-19: An Open-Label Randomized Controlled Pilot Study

18 patient bromhexine late treatment RCT: 75% higher hospital discharge (p=0.11) and 3% slower recovery.
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.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12881, https://c19p.org/li5

5. Tolouian et al., Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial

372 patient bromhexine prophylaxis RCT: 70% lower hospitalization (p=0.15), 53% fewer symptomatic cases (p=0.007), and 50% fewer cases (p=0.03).
PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Dec 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3989849, https://c19p.org/tolouian2

6. Mareev et al., Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)

66 patient bromhexine late treatment RCT: 11% improved recovery (p=0.47), 8% shorter hospitalization (p=0.35), and 87% improved viral clearance (p=0.08).
Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareev

7. Tolouian et al., Effect of bromhexine in hospitalized patients with COVID-19

100 patient bromhexine late treatment RCT: 76% lower mortality (p=0.43), 76% greater improvement (p=0.43), and 75% worse viral clearance (p=0.02).
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). The very large difference between unadjusted and adjusted results is due to much higher risk for patients with renal disease and the much higher prevalence of renal disease in the bromhexine group. The study also shows 90% of patients in the control group had BMI>=30 compared to 0% in the treatment group, suggesting a possible problem with randomization. Due to the imbalance between groups, results were adjusted for BMI>30, smoking, and renal disease. 11 patients were lost to followup in the treatment group compared to zero in the control group, perhaps in part due to faster recovery in the treatment group. 9 patients were excluded from the treatment group because they did not want to take bromhexine after discharge. Therefore up to 29% of treatment..
Mar 2021, J. Investig. Med., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970656/, https://c19p.org/tolouian

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