Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia

In the current situation it is of great importance to discover a safe, cost-effective and available treatment strategy in order to limit the rapidly spreading SARS-Cov-2. Recent studies have shown that hydroxychloroquine could have a role in the treatment of infected patients. It is however not very likely that hydroxychloroquine alone could be adequate for treatment of Covid-19 disease. Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients.

Hypothesis

1. Combined treatment with bromhexin and hydroxychloroquine shortens the course of disease in hospitalized Covid-19 patients compared to hydroxychloroquine alone.
2. Combined treatment with bromhexin and hydroxychloroquine lowers the incidence of secundary pulmonary infections in hospitalized Covid-19 patients compared to hydroxychloroquine alone.
3. Combined treatment with bromhexin and hydroxychloroquine decreases the need for ICU admission in hospitalized Covid-19 patients compared to hydroxychloroquine alone.

Study Overview

• Status: Unknown
• Conditions: Covid-19
• Intervention / Treatment: Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Miha Mežnar; Phone Number: +386 3 4233419; Email: meznar.miha@gmail.com
• Study Contact Backup: Name: matej Podbregar; Phone Number: +386 3 4233418; Email: matej.podbregar@sb-celje.si

Study Locations

• Slovenia
  • Celje, Slovenia, 3000
    • Recruiting
    • SB Celje
    • Contact: Miha Mežnar; Phone Number: +386 3 4233419; Email: meznar.miha@gmail.com
    • Contact: Matej Podbregar; Phone Number: +386 3 4233419; Email: matej.podbregar@sb-celje.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 18 years,
• confirmed infection (positive PCR from nasopharyngeal swab),
• fullfilled hospital admission criteria

Exclusion Criteria:

• pregnancy,
• known allergy for bromhexine or hydroxychloroquine,
• epilepsy,
• prolonged QTc interval,
• Child C liver disease,
• dementia,
• psychoorganic syndrome,
• terminal chronic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hydroxychloroquine and bromhexine; Bromhexine 16 mg TID + hydroxychloroquine 200 mg BID	Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet; bromhexine 16 mg TID hydroxychloroquine 200 mg BID; Other Names: hydroxychloroquine
Active Comparator: hydroxychloroquine alone; hydroxychloroquine 200 mg BID	Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet; bromhexine 16 mg TID hydroxychloroquine 200 mg BID; Other Names: hydroxychloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of hospitalization	number of days the patient is treated in the hospital	through study completion, an average of 6 months
Duration of disease	Number of days from the onset of symptoms to hospital discharge	through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital-aquired pneumonia	Incidence of HAP	through study completion, an average of 6 months
ICU stay duration	Number of days spent in the ICU	through study completion, an average of 6 months
Oxygene therapy duration	number of days on oxygene therapy	through study completion, an average of 6 months
Mechanical ventilatory support duration	Number of hours on mechanical ventilation	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: General and Teaching Hospital Celje

Study record dates

Study Major Dates

• Study Start (Anticipated): April 10, 2020
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): July 31, 2020

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 18, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 18, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Expectorants; Hydroxychloroquine; Bromhexine
• Other Study ID Numbers: SBCebromhexinCovid-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No