A Randomized, Multi-centric, Double-blind, Placebo-controlled study to Evaluate the Efficacy and Safety of Bromhexine, a serine protease (TMPRSS2) blocker, to prevent COVID-19

To evaluate the safety and efficacy of bromehexine in post exposure prophylaxis against COVID-19

Clinical trial with controlled group, parallel design, double-blinded, multi-centric, randomized; phase 3 on 1050 patients. Randomization of the patients will be conducted using block randomization method via Rand function in Excel software.

The present study will be conducted at Imam Hossein, Shahid Labafinejad, Shohadaye Gomnam Medical Centers affiliated to Shahid Beheshti University of Medical Sciences, Tehran. The study designed as double blinded in which the participants and outcome assessors will be masked to their assignment.

Inclusion criteria: Individuals who have the ability to understand and desire to sign the informed consent; Age of 18 years or more; Exposure and close contact with a COVID-19 patients within 4 days before entering the study; must agree not to enroll in another study prior to completion of Day 14 of study. Non inclusion criteria: individuals with low risk of exposure (wearing a face mask and an eye shield); individuals with exposure time of less than 15 minutes; patients who receive medication for prophylaxis or treatment if COVID-19; patients with any sign and symptoms of COVID-19; Taking the medication for less than 3 days; COVID-19 compatible symptoms on day 1.

Intervention group: patients will receive Bromhexine 8mg 3 times a day for 14 days. Control group: patients will receive placebo 3 times a day for 14 days.

Incidence of COVID-19 disease; COVID-19 disease severity

In this update, we considered adding exclusion criteria to the record. based on the blinding of the statistical analyzers and outcome assessors, these two changes have been made. an interim analysis has been considered. considering the blinding strategy in this study, we blinded the outcome assessors and statistical analyzers from the study allocation. because of the incidence of the COVID-19 compatible symptoms in the 1st day in some patients and also some patients didn't take the medications as ordered, these two exclusion criteria have been considered. an interim analysis to assess the outcome occurrence is considered.

Randomization will be recorded on an Excel file by the principal investigator. Participants will be randomized via permuted block randomization. Each block will be consistent of variable sizes of 4 or 6 or 8 patients. For assignment of each patient to the drug or placebo group, for each patients a unique code consistent of 2 letters and a digit will be assigned. the code will be unique for each patient ( for example code AB1 for first patient). Only the principle investigator will be informed of the assignment of each code to the medication or placebo group.

Participants will be provided masked study medicine, directly in research centers or shipped by courier service. The intervention vs. placebo will not be identical; however, participants and outcome assessors will be masked to their assignment.

Primary and secondary outcome data after making participants unrecognizable will be released

6 months after publishing the results of primary outcome

Any researchers will have access to the data after allowance of corresponding author

Performing any analysis to any data resulted form this study will be allowed only with the permission of corresponding author

Correspondance author

After requesting for data, correspondence will check the authorization and then they will be informed about it