New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial)

Granados-Montiel et al., BMJ Open, doi:10.1136/bmjopen-2020-045190, ELEVATE, NCT04340349, Jun 2021

https://c19early.org/granadosmontielbb.html

Estimated 214 participant bromhexine + HCQ prophylaxis RCT with results not reported over 3 years after estimated completion.

Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants1,2.

2 bromhexine RCTs have results missing long after expected3,4
The trials report an estimated total of 304 patients.

Important missing comments or errors? Let us know.

Study covers TMPRSS2 inhibitors, bromhexine, and HCQ.

1. Willett et al., The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism, medRxiv, doi:10.1101/2022.01.03.21268111.medrxiv.org, doi.org.

2. Peacock et al., The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry, bioRxiv, doi:10.1101/2021.12.31.474653.biorxiv.org, doi.org.

3. Granados-Montiel et al., New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial), BMJ Open, doi:10.1136/bmjopen-2020-045190.bmj.com, doi.org.

4. Mežnar et al., Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia, NCT04355026, clinicaltrials.gov/study/NCT04355026.clinicaltrials.gov.

Granados-Montiel et al., 30 Jun 2021, Double Blind Randomized Controlled Trial, placebo-controlled, Mexico, peer-reviewed, this trial uses multiple treatments in the treatment arm (combined with HCQ) - results of individual treatments may vary, trial NCT04340349 (history) (ELEVATE). Contact: juliogram@gmail.com.

This Paper Bromhexine All

DOI record: { "DOI": "10.1136/bmjopen-2020-045190", "ISSN": [ "2044-6055", "2044-6055" ], "URL": "http://dx.doi.org/10.1136/bmjopen-2020-045190", "abstract": "IntroductionSARS-CoV-2 infection in Mexico has caused ~2.7 million confirmed cases; around 20%–25% of health workers will be infected by the virus at their workplace, with approximately 4.4% of mortality. High infectivity of SARS-CoV-2 is related with cell entry mechanism, through the ACE receptor. SARS-CoV-2 requires transmembrane protease serine 2 to cleave its spike glycoprotein and ensure fusion of host cell and virus membrane. We propose studying prophylactic treatment with hydroxychloroquine (HCQ) and bromhexine (BHH), which have been shown to be effective in preventing SARS-CoV-2 infection progression when administered in early stages. The aim of this study is to assess the efficacy of HCQ and BHH as prophylactic treatments for SARS-CoV-2 infection in healthy health workers exposed to the virus.Methods and analysisDouble-blind randomised clinical trial, with parallel allocation at a 1:1 ratio with placebo, of low doses of HCQ plus BHH, for 60 days. Study groups will be defined as follows: (1) HCQ 200 mg/day+BHH 8 mg/8 hours versus (2) HCQ placebo plus BHH placebo. Primary endpoint will be efficacy of both interventions for the prevention of SARS-CoV-2 infection, determined by the risk ratio of infected personnel and the absolute risk. At least a 16% reduction in absolute risk is expected between the intervention and placebo groups; a minimum of 20% infection is expected in the placebo group. The sample size calculation estimated a total of 214 patients assigned: two groups of 107 participants each.Ethics and disseminationThis protocol has been approved by the local Medical Ethics Committee (National Institute of Rehabilitation ‘Luis Guillermo Ibarra Ibarra’, approval number INRLGII/25/20) and by the Federal Commission for Protection against Sanitary Risks (COFEPRIS, approval number 203 300 410A0058/2020). The results of the study will be submitted for publication in peer-reviewed journals and disseminated through conferences.Trial registration numberNCT04340349.", "alternative-id": [ "10.1136/bmjopen-2020-045190" ], "author": [ { "ORCID": "http://orcid.org/0000-0002-0611-6421", "affiliation": [], "authenticated-orcid": false, "family": "Granados-Montiel", "given": "Julio", "sequence": "first" }, { "affiliation": [], "family": "Hazan-Lasri", "given": "Eric", "sequence": "additional" }, { "affiliation": [], "family": "Franco-Cendejas", "given": "Rafael", "sequence": "additional" }, { "affiliation": [], "family": "Chávez-Heres", "given": "Tatiana", "sequence": "additional" }, { "affiliation": [], "family": "Silva-Bermudez", "given": "Phaedra", "sequence": "additional" }, { "affiliation": [], "family": "Aguilar-Gaytán", "given": "Rocio", "sequence": "additional" }, { "affiliation": [], "family": "Manzano-León", "given": "Natalia", "sequence": "additional" }, { "affiliation": [], "family": "Méndez-Maldonado", "given": "Karla", "sequence": "additional" }, { "affiliation": [], "family": "Alvarez-Arce", "given": "Alejandro", "sequence": "additional" }, { "affiliation": [], "family": "Martínez-Portilla", "given": "Raigam Jafet", "sequence": "additional" } ], "clinical-trial-number": [ { "clinical-trial-number": "nct04340349", "registry": "10.18810/clinical-trials-gov", "type": "preResults" } ], "container-title": "BMJ Open", "container-title-short": "BMJ Open", "content-domain": { "crossmark-restriction": true, "domain": [ "bmj.com" ] }, "created": { "date-parts": [ [ 2021, 8, 3 ] ], "date-time": "2021-08-03T16:33:23Z", "timestamp": 1628008403000 }, "deposited": { "date-parts": [ [ 2021, 8, 3 ] ], "date-time": "2021-08-03T16:33:57Z", "timestamp": 1628008437000 }, "funder": [ { "award": [ "SECTEI/061/2020" ], "name": "Secretaría de Educación, Ciencia, Tecnologia e Inovacion de la Ciudad de México" } ], "indexed": { "date-parts": [ [ 2022, 5, 17 ] ], "date-time": "2022-05-17T13:34:05Z", "timestamp": 1652794445370 }, "is-referenced-by-count": 1, "issue": "8", "issued": { "date-parts": [ [ 2021, 8 ] ] }, "journal-issue": { "issue": "8", "published-online": { "date-parts": [ [ 2021, 8, 3 ] ] }, "published-print": { "date-parts": [ [ 2021, 8 ] ] } }, "language": "en", "license": [ { "URL": "http://creativecommons.org/licenses/by-nc/4.0/", "content-version": "unspecified", "delay-in-days": 2, "start": { "date-parts": [ [ 2021, 8, 3 ] ], "date-time": "2021-08-03T00:00:00Z", "timestamp": 1627948800000 } } ], "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1136/bmjopen-2020-045190", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "239", "original-title": [], "page": "e045190", "prefix": "10.1136", "published": { "date-parts": [ [ 2021, 8 ] ] }, "published-online": { "date-parts": [ [ 2021, 8, 3 ] ] }, "published-print": { "date-parts": [ [ 2021, 8 ] ] }, "publisher": "BMJ", "reference": [ { "key": "2021080308551899000_11.8.e045190.1", "unstructured": "C.DM . 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