Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial

Abstract

Introduction: Bromhexine is a potential therapeutic option in COVID-19, but no data from a randomized clinical trial has been available. The present study aimed to evaluate the efficacy of bromhexine in intensive care unit (ICU) admission, mechanical ventilation, and mortality in patients with COVID-19. Methods: An open-label randomized clinical trial study was performed in Tabriz, North-West of Iran. They were randomized to either the treatment with the bromhexine group or the control group, in a 1:1 ratio with 39 patients in each arm. Standard therapy was used in both groups and those patients in the treatment group received oral bromhexine 8 mg three times a day additionally. The primary outcome was a decrease in the rate of ICU admissions, intubation/mechanical ventilation, and mortality. Results: A total of 78 patients with similar demographic and disease characteristics were enrolled. There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006), intubation (1 out of 39 vs. 9 out of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. No patients were withdrawn from the study because of adverse effects. Conclusion: The early administration of oral bromhexine reduces the ICU transfer, intubation, and the mortality rate in patients with COVID-19. This affordable medication can easily be administered everywhere with a huge positive impact(s) on public health and the world economy. Altogether, the verification of our results on a larger scale and different medical centers is strongly recommended. Trial Registration: IRCT202003117046797N4; https://irct.ir/trial/46969.

Ambroxol and Ciprofloxacin Show Activity Against SARS-CoV2 in Vero E6 Cells at Clinically-Relevant Concentrations

“…However, in our hands, AMB appears to have a separate and distinct antiviral activity from that of BHX, with BHX being hypothesized 24 and trialed 25 as a repurposed treatment for COVID-19.…”

An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19

“… 25 It has also been included as a potential drug repurposing TMPRSS2 inhibitor and been shown to reduce the ICU admissions, intubation, and mortality rate in patients with COVID19 in a 78 patient open-label, randomized clinical trial. 27 , 40 , 41 Unfortunately, few details of the assay utilized, scale of assay, or its development were described, but the substrate identified in our study as the most amenable for HTS (Boc-Gln-Ala-Arg-AMC) was also used in the Lucas et al study. Notably, we did not detect inhibition of TMPRSS2 from BHH, and confirmed 99.9% purity of our BHH sample ( Supplementary Figure 3 ).…”

SARS-CoV-2 and SARS-CoV spike-mediated cell-cell fusion differ in the requirements for receptor expression and proteolytic activation

“…Irrespective of the role of cell-cell fusion in COVID-19, in light of the observed paradoxical activation of cell-cell fusion by Bromhexine and its lack of inhibitory activity against entry of SARS-CoV-2 spike-pseudotyped lentiviruses on TMPRSS2 expressing cells, we would at the moment caution against clinical use of Bromhexine for treatment or prophylaxis of COVID-19, at least at higher concentrations that aim at the inhibition of TMPRSS2. A recent small randomized trial showed promising results for Bromhexine at 3x 8 mg per day combined with hydroxychloroquine (48), which should result in Bromhexine plasma concentrations in the range of 0.1 µM (49). We are fairly confident to postulate that these favorable results are unlikely due to inhibition of TMPRSS2, although we can’t fully exclude extremely weak activity.…”