Low-dose Hydroxychloroquine and Bromhexine: a Novel Regimen for COVID-19 Prophylaxis in Healthcare Professionals

Study Overview
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Brief Summary
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This study will investigate the security and efficacy of a daily low dose of hydroxychloroquine and Bromhexine, in preventing the development of the disease from COVID-19 in Health Care Workers at a National Institute of Health In Mexico City.

Detailed Description
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This study will combine two drugs (hydroxychloroquine and Bromhexine) to see if hydroxychloroquine is better in combination with Bromhexine in preventing the development of the disease from COVID-19 in Health Care Workers at a National Institute of Health In Mexico City. Hydroxychloroquine will be used in a low dose (200 mg every 24 hrs). Bromhexine will be 8mg every 8 hrs. The study groups will be the following: 1) HCQ 200mg/d + BHH placebo 2) HCQ placebo plus BHH placebo

Official Title
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Low-dose Hydroxychloroquine and Bromhexine: a Novel Regimen for COVID-19 Prophylaxis in Healthcare Professionals (ELEVATE Trial)

Conditions
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Hydroxychloroquine, Antimalarials, Enzyme Inhibitors, Antirheumatic Agents

Intervention / Treatment
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* Drug: Hydroxychloroquine Sulfate
* Drug: Bromhexine 8 MG


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Health personnel working at INR LGII or INCMNSZ who wish to participate in the study and sign the informed consent. Over 18 and under 60 years of age, both genders. Contacting with suspected or confirmed SARS-CoV-2 infection. Normal electrocardiogram. Exclusion criteria Positive quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) test for SARS-CoV-2 at the time of inclusion. Panel of IgG or IgM antibodies positive for SARS-CoV-2 at the time of inclusion. Development of respiratory symptoms suspicious of SARS-CoV-2 infection during the first 7 days after treatment is initiated, confirmed by qRT-PCR and IgG or IgM antibodies postiver for SARS-CoV-2. History of allergies to any hydroxychloroquine or bromhexine related compound or medication. Use of immunosuppressors for any reason. History of bone marrow transplant. Known glucose-6-phosphate dehydrogenase deficiency. Chronic kidney disease or glomerular filtration <20ml/min. Use of other drugs with reported pharmacological interactions (i.e., digitalis, flecainide, amiodarone, procainamide, or propafenone). History of long QT syndrome. Electrocardiogram with QTc>500 msec. Pregnant or breastfeeding personnel. Epilepsy. Known liver disease. Personnel who have received the Covid-19 vaccine Elimination criteria Personnel who decide to leave the study for any reason not related to adverse events. Personnel with incomplete information on the primary outcome (qRT-PCR for SARS-CoV-2). Personnel who are relocated to work in another institution. Personnel who do not wish to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Hydroxychloroquine plus Bromhexine<br>200 mg of Hydroxychloroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months | Drug: Hydroxychloroquine Sulfate<br>* A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor.<br>* Other names: Evoquin;Drug: Bromhexine 8 MG<br>* TMPRSS2 blocker<br>* Other names: Bisolvon;|
| Placebo Comparator: Hydroxychloroquine plus Bromhexine<br>200 mg of Hydroxycholoroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months | Drug: Hydroxychloroquine Sulfate<br>* A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor.<br>* Other names: Evoquin;Drug: Bromhexine 8 MG<br>* TMPRSS2 blocker<br>* Other names: Bisolvon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of the expression of mRNA SARS-CoV-2 and presence or absence of antibodies anti-SARS-CoV-2 | Primary endpoint will be the proportion of health personnel infected by SARS-CoV-2 at day 60 after starting treatment, in both groups. The infection will be diagnosed using qRT-PCR for relative expression of the mRNA of SARS-CoV-2 and the measure of IgM and IgG antibodies anti-SARS-CoV-2 after day 7 of treatment using rapid test Cellex qSARS-CoV-2 IgG/IgM | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of the expression of mRNA SARS-CoV-2 and presence or absence of antibodies anti-SARS-CoV-2 | The secondary endpoint will be the proportion of health personnel infected 90 days after starting treatment in both groups. The infection will be diagnosed using qRT-PCR for relative expression of the mRNA of SARS-CoV-2 and the measure of IgM and IgG antibodies anti-SARS-CoV-2 after day 7 of the start of treatment using rapid test Cellex qSARS-CoV-2 IgG/IgM | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, COVID-19, Hydroxychloroquine, BROMHEXINE