Effect of bromhexine in hospitalized patients with COVID-19
et al., J. Investig. Med., doi:10.1136/jim-2020-001747
, Effect of bromhexine in hospitalized patients with COVID-19, J. Investig. Med., doi:10.1136/jim-2020-001747
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 patients may have been excluded because they recovered quickly.Bromhexine may be less effective for omicron due to the entry process moving towards TMPRSS2-independent fusion.
|
risk of death, 76.0% lower, OR 0.24, p = 0.43, treatment 48, control 52, adjusted per study, Table 3, RR approximated with OR.
|
|
risk of no improvement, 75.9% better, OR 0.24, p = 0.43, treatment 48, control 52, adjusted per study, inverted to make OR<1 favor treatment, Table 2, RR approximated with OR.
|
|
risk of no viral clearance, 74.5% higher, RR 1.75, p = 0.02, treatment 29 of 48 (60.4%), control 18 of 52 (34.6%), mid-recovery day 7.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Tolouian et al., 15 Mar 2021, Randomized Controlled Trial, Iran, peer-reviewed, 7 authors.
Abstract: Original research
Effect of bromhexine in hospitalized patients
with COVID-19
Ramin Tolouian ,1 Zuber D Mulla ,2 Hamidreza Jamaati,3
Abdolreza Babamahmoodi,4 Majid Marjani,5 Raha Eskandari,3 Farzaneh Dastan6
For numbered affiliations see
end of article.
Correspondence to
Dr Farzaneh Dastan,
Department of Clinical
Pharmacy, School of
Pharmacy, Shahid Beheshti
University of Medical
Sciences, Tehran, Iran;
fzh.dastan@gmail.com
Accepted 24 February 2021
© American Federation for
Medical Research 2021.
No commercial re-use. See
rights and permissions.
Published by BMJ.
To cite: Tolouian R,
Mulla ZD, Jamaati H,
et al. J Investig Med Epub
ahead of print: [please
include Day Month Year].
doi:10.1136/jim-2020001747
ABSTRACT
Background Bromhexine is a potent inhibitor
of transmembrane serine protease 2 and appears
to have an antiviral effect in controlling influenza
and parainfluenza infection; however, its efficacy in
COVID-19 is controversial.
Methods A group of hospitalized patients with
confirmed COVID-19 pneumonia were randomized
using 1:1 allocation to either standard treatment
lopinavir/ritonavir and interferon beta-1a or
bromhexine 8 mg four times a day in addition to
standard therapy. The primary outcome was clinical
improvement within 28 days, and the secondary
outcome measures were time to hospital discharge,
all-cause mortality, duration of mechanical
ventilation, the temporal trend in 2019-nCoV reverse
transcription-polymerase chain reaction positivity
and the frequency of adverse drug events within 28
days from the start of medication.
Results A total of 111 patients were enrolled in
this randomized clinical trial and data from 100
patients (48 patients in the treatment arm and 52
patients in the control arm) were analyzed. There
was no significant difference in the primary outcome
of this study, which was clinical improvement. There
was no significant difference in the average time
to hospital discharge between the two arms. There
were also no differences observed in the mean
intensive care unit stay, frequency of intermittent
mandatory ventilation, duration of supplemental
oxygenation or risk of death by day 28 noted
between the two arms.
Conclusion Bromhexine is not an effective
treatment for hospitalized patients with COVID-19.
The potential prevention benefits of bromhexine
in asymptomatic postexposure or with mild
infection managed in the community remain to be
determined.
Late treatment
is less effective
is less effective
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.