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

Sponsor

Instituto Nacional de Rehabilitacion (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04340349

Collaborator

(none)

214

Enrollment

Location

Arms

4.9

Anticipated Duration (Months)

43.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hydroxychloroquine Antimalarials Enzyme Inhibitors Antirheumatic Agents	Drug: Hydroxychloroquine Sulfate Drug: Bromhexine 8 MG	Early Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

214 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

DOUBLE BLINDED

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 1, 2021

Actual Primary Completion Date :

May 30, 2021

Anticipated Study Completion Date :

Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: Hydroxychloroquine plus Bromhexine 200 mg of Hydroxychloroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months	Drug: Hydroxychloroquine Sulfate A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor. Other Names: Evoquin Drug: Bromhexine 8 MG TMPRSS2 blocker Other Names: Bisolvon
Placebo Comparator: Hydroxychloroquine plus Bromhexine 200 mg of Hydroxycholoroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months	Drug: Hydroxychloroquine Sulfate A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor. Other Names: Evoquin Drug: Bromhexine 8 MG TMPRSS2 blocker Other Names: Bisolvon

Arm

Intervention/Treatment

Experimental: Experimental: Hydroxychloroquine plus Bromhexine

200 mg of Hydroxychloroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months

Drug: Hydroxychloroquine Sulfate

A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor.

Other Names:

Evoquin

Drug: Bromhexine 8 MG

TMPRSS2 blocker

Other Names:

Bisolvon

Placebo Comparator: Hydroxychloroquine plus Bromhexine

200 mg of Hydroxycholoroquine daily for 2 months 8 mg of Bromhexine every 8 hrs for 2 months

Drug: Hydroxychloroquine Sulfate

A daily low dose of Hydroxychloroquine Sulfate. Increase the endosomal pH and inhibits of ACE2 glycosylation receptor.

Other Names:

Evoquin

Drug: Bromhexine 8 MG

TMPRSS2 blocker

Other Names:

Bisolvon

Outcome Measures

Primary Outcome Measures

Quantification of the expression of mRNA SARS-CoV-2 and presence or absence of antibodies anti-SARS-CoV-2 [Day 60]
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

Secondary Outcome Measures

Quantification of the expression of mRNA SARS-CoV-2 and presence or absence of antibodies anti-SARS-CoV-2 [Day 90]
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

Other Outcome Measures

Positive SARS-CoV-2 result during the treatment [Day 30 and day 90]
The proportion of health personnel positive for SARS-CoV-2 and result in the need for oxygen use, admission to the intensive care unit (ICU), presence of pneumonia by computer tomography scan (CT), death, severe pneumonia defined by the American Thoracic Association, time from hospitalization to recovery in days.
Adverse events [Day 60]
The proportion of health personnel presenting any of the following during the study period: death, nausea, vomiting, abdominal pain, diarrhea, rash, itchy skin, hair loss, lengthening of the QT interval in the electrocardiogram (>500msec), corneal opacity, cardiac arrhythmias, heart failure or kidney failure (renal clearance <20ml/min). The proportion of the compound of adverse events between the groups will be analyed using RR and ARI for 60 days with their respective 95% confidence intervals

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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