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)
Dr Julio Granados-Montiel, Eric Hazan-Lasri, Rafael Franco-Cendejas, Tatiana Chávez-Heres, Phaedra Silva-Bermudez, Rocio Aguilar-Gaytán, Natalia Manzano-León, Karla Méndez-Maldonado, Alejandro Alvarez-Arce, Raigam Jafet Martínez-Portilla
BMJ Open, doi:10.1136/bmjopen-2020-045190
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).
Competing interests None declared. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required.
Ethics approval The approval of the research ethics committee of the INR-LGII of Mexico has been obtained. Provenance and peer review Not commissioned; externally peer reviewed.
Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by-nc/ 4. 0/.
ORCID iD Julio Granados-Montiel http:// orcid. org/ 0000-0002-0611-6421
References
22 Geleris, Sun, Platt, Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2012410
Baig, Khaleeq, Ali, Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms, ACS Chem Neurosci,
doi:10.1021/acschemneuro.0c00122
Chude, Amaravadi, Targeting autophagy in cancer: update on clinical trials and novel inhibitors, Int J Mol Sci,
doi:10.3390/ijms18061279
Depfenhart, De Villiers, Lemperle, Potential new treatment strategies for COVID-19: is there a role for bromhexine as add-on therapy?, Intern Emerg Med,
doi:10.1007/s11739-020-02383-3
Dm, COVID-19 dashboard México
Dutta, Sharma, Sharma, Short-Term hydroxychloroquine in COVID-19 infection in people with or without metabolic syndrome -clearing safety issues and good clinical practice, Eur Endocrinol,
doi:10.17925/EE.2020.16.2.109
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends,
doi:10.5582/bst.2020.01047
Han, Ma, Li, Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors, Emerg Microbes Infect,
doi:10.1080/22221751.2020.1770129
Helal, Gad, Mohamed Fahmy Abd-Ellah and Mse. hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in Genotype-4 chronic hepatitis C patients, Antivir Ther
Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell,
doi:10.1016/j.cell.2020.02.052
Juurlink, Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection, CMAJ,
doi:10.1503/cmaj.200528
Levy, Yagil, Bursztyn, Ace2 expression and activity are enhanced during pregnancy, Am J Physiol Regul Integr Comp Physiol,
doi:10.1152/ajpregu.90592.2008
Li, Wang, Asymptomatic and human-to-human transmission of SARS-CoV-2 in a 2-Family cluster, Emerg Infect Dis,
doi:10.3201/eid2607.200718
Mareev, Orlova, Pavlikova, Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT), Kardiologiia,
doi:10.18087/cardio.2020.8.n1307
Pal, Berhanu, Desalegn, Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): an update, Cureus,
doi:10.7759/cureus.7423
Ravi, Cortade, Ng, Diagnostics for SARS-CoV-2 detection: a comprehensive review of the FDA-EUA COVID-19 testing landscape, Biosensors and Bioelectronics,
doi:10.1016/j.bios.2020.112454
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res,
doi:10.1038/s41422-020-0282-0
Wang, Lin, Huang, Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery, Journal of Interferon & Cytokine Research,
doi:10.1089/jir.2014.0038
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China, JAMA,
doi:10.1001/jama.2020.2648
Xu, Zhong, Deng, High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa, Int J Oral Sci,
doi:10.1038/s41368-020-0074-x
Yao, Ye, Zhang, In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Infect Dis,
doi:10.1093/cid/ciaa237
Zahr, Urien, Llopis, Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19, Therapie,
doi:10.1016/j.therap.2021.01.056
Zanasi, Mazzolini, Kantar, A reappraisal of the mucoactive activity and clinical efficacy of bromhexine, Multidiscip Respir Med,
doi:10.1186/s40248-017-0088-1