lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial

15 Pages Posted: 20 Dec 2021

See all articles by Ramin Tolouian

Ramin Tolouian

Southern Arizona VA Health Care System and University of Arizona College of Medicine

Omid Moradi

Shahid Beheshti University of Medical Sciences

Zuber D. Mulla

Texas Tech University Health Sciences Center

Shadi Ziaie

Shahid Beheshti University of Medical Sciences

Mehrdad Haghighi

Shahid Beheshti University of Medical Sciences - Infectious Diseases and Tropical Medicine Research Center

Hadi Esmaily

Shahid Beheshti University of Medical Sciences

Hossein Amini

Shahid Beheshti University of Medical Sciences

Rezvan Hassanpour

Shahid Beheshti University of Medical Sciences

Elham Pourheidar

Shahid Beheshti University of Medical Sciences

Mehran Kouchek

Shahid Beheshti University of Medical Sciences

Alireza Manafi-Rasi

Shahid Beheshti University of Medical Sciences

Shahnaz Sali

Shahid Beheshti University of Medical Sciences

Sara Abolghasemi

Shahid Beheshti University of Medical Sciences

Shabnam Tehrani

Shahid Beheshti University of Medical Sciences

Audrey C. Tolouian

The University of Texas

Mohammad Sistanizad

Shahid Beheshti University of Medical Sciences

More...

Abstract

Background: Limited number of medications are available for the post-exposure prophylaxis of COVID-19 infection. Whether bromhexine can prevent or mitigate symptomatic infection after virus exposure is undetermined.

Methods: A multi-center randomized; double-blind, placebo-controlled clinical trial was conducted. The 372 adults (≥18 years) who had close contact within 4 days with a household member with confirmed COVID-19 were randomly assigned to receive bromhexine (n=187) or placebo (n=185) three times a day for two weeks. The primary outcome was the incidence of symptomatic COVID-19. Secondary outcomes included the incidence of hospitalization or death, the incidence of confirmed COVID-19 detection by PCR in symptomatic patients and presence of adverse drug reactions.

Findings: The incidence of symptomatic COVID-19 was significantly lower in individuals who received bromhexine than in those who received the placebo (16 [8.6%] vs 34 [18.4%], relative risk=0.47, p=0.005). PCR-confirmation was reported in 13 (7.0%) and 26 (14.1%) of the individuals in the bromhexine and placebo groups, respectively ( p= 0.025), with a relative risk reduction of 50%. The hospitalization rate, death and medication side effects did not vary significantly between the bromhexine or placebo arms.

Interpretation: Bromhexine is an effective, non-invasive, and affordable agent with a low side-effect profile to prevent symptomatic COVID-19. Early use of bromhexine potentially provides another layer of protection and hence it can play a prominent role in ending the pandemic especially given the emergence of new variants and the vaccination challenges faced by developing countries.

Trial Registration: The trial was registered with the Iranian Registry of Clinical
Trials (https://www.irct.ir/), a primary registry in the World Health Organization network, registration code IRCT20120703010178N22.

Funding: Primary funding sourceOffice of Deputy of Research and Technology, SBUMS, Tehran, Iran.

Declaration of Interest: Nothing to report except Dr. Ramin Tolouian received speaker honorarium from Sanofi-Genzyme and consulting fee from Travere therapeutics.

Ethical Approval: The trial was conducted from December 21, 2020, to July 25, 2021, in four medical centers, in Tehran, Iran. The
trial was approved by the ethics committee review board at the Shahid Beheshti University of Medical Sciences with
the code of IR.SBMU.PHARMACY.REC.1399.247.

Keywords: COVID-19, Bromhexine, Post exposure, Prophylaxis, Symptomatic disease, Clinical trial, TMPRSS2

Suggested Citation

Tolouian, Ramin and Moradi, Omid and Mulla, Zuber D. and Ziaie, Shadi and Haghighi, Mehrdad and Esmaily, Hadi and Amini, Hossein and Hassanpour, Rezvan and Pourheidar, Elham and Kouchek, Mehran and Manafi-Rasi, Alireza and Sali, Shahnaz and Abolghasemi, Sara and Tehrani, Shabnam and Tolouian, Audrey C. and Sistanizad, Mohammad, Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial. Available at SSRN: https://ssrn.com/abstract=3989849 or http://dx.doi.org/10.2139/ssrn.3989849

Ramin Tolouian

Southern Arizona VA Health Care System and University of Arizona College of Medicine ( email )

United States

Omid Moradi

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Zuber D. Mulla

Texas Tech University Health Sciences Center ( email )

United States

Shadi Ziaie

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Mehrdad Haghighi

Shahid Beheshti University of Medical Sciences - Infectious Diseases and Tropical Medicine Research Center ( email )

Tehran
Iran

Hadi Esmaily

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Hossein Amini

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Rezvan Hassanpour

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Elham Pourheidar

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Mehran Kouchek

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Alireza Manafi-Rasi

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Shahnaz Sali

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Sara Abolghasemi

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Shabnam Tehrani

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Audrey C. Tolouian

The University of Texas ( email )

Mohammad Sistanizad (Contact Author)

Shahid Beheshti University of Medical Sciences ( email )

Velenjak Street, Shahid Chamran High Way
Tehran
Iran

Click here to go to TheLancet.com

Paper statistics

Abstract Views
1,074
Downloads
136
PlumX Metrics