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

Abstract

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-centre 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 enrollment 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; and 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 COVID-19 (ClinicalTrials.gov number, NCT04405999).

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

“…It was not possible to obtain the translation from Ct values to the number of viral copies, so comparison to viral loads reported in other studies is not possible. However, in other studies of bromhexine in hospitalized patients [12,13] or medical personnel [14], viral loads were not measured. In a protocol for systemic review and meta-analysis to assess the efficacy and safety of bromhexine hydrochloride tablets in treated pediatric COVID-19, assessment of viral load was not included among the types of outcome measures [23].…”

“…No previous clinical trials with bromhexine in patients with COVID-19 have been carried out in Spain, and there is limited evidence of the efficacy of this drug in the literature, the usefulness of which remains controversial [10][11][12][13][14]. Despite the recognition of the pharmaceutical properties of bromhexine to inhibit TMPRSS2 and its potential role in treating or preventing SARS-CoV-2 infection [10,16,[18][19][20][21], expectations of efficacy in clinical practice appeared to be disappointing, which are consistent with findings of the present study.…”

“…In contrast, in another randomized open-label study of 78 patients, the early administration of bromhexine (8 mg four times daily) for 2 weeks in addition to standard therapy reduced the need for ICU admission, intubation/mechanical ventilation, and 28-day mortality [13]. In a randomized open-label study of medical staff actively involved in the care of patients with suspected or confirmed SARS-CoV-2 infection, prophylactic treatment with bromhexine (8 mg three times daily) was associated with fewer participants who developed symptomatic COVID-19 as compared to controls, although differences in positive swab PCR test or signs of clinical infection at day 28 were not found [14].…”

Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview

“…A significant decrease in the rate of ICU admission and need for ventilation after BHH administration was established in patients with COVID-19 symptoms [ 110 ]. Prophylactic BHH intake was investigated in a non-peer-reviewed study that showed a connection between BHH prophylaxis and a reduced rate of symptomatic COVID-19 infection but showed no relevance in the lowering combined primary endpoint rate, a positive swab PCR test, or COVID-19 [ 111 ]. A non-significant trend toward better clinical recovery upon administration of BHH was reported by Li et al [ 112 ].…”

COVID-19 Drug Development: Role of Drug Repurposing

“…Repurposing a medicine involves using it for a different indication after having it licensed by a regulatory body like the FDA, the European Medicines Agency (EMA), or the Medicines and Healthcare Products Regulatory Agency (MHRA), among others. Many pharmaceutical companies are presently using drug repurposing to regenerate some of their FDA-approved and previously unsuccessful pipeline molecules as novel medicines for a variety of illness conditions due to the enormous promise of a reduced development cycle [13,14].…”