Outpatient Treatment With CoVid-19 With Prexablu

Summary

Within the epidemic context of phase 3 in Mexico, the implementation of new treatments that have been shown to be beneficial for patients in other countries is an urgent need. Methylene blue (MB, the oxidized form, blue color) has been used in many different clinical medicine areas, ranging from malaria to orthopedics. Methylene blue absorbs energy directly from a light source and then transfers this energy to molecules of oxygen creating singlet oxygen (O2), which is the first electronic excited state of molecular oxygen (O2). Singlet oxygen is extremely electrophilic; thus, it can directly oxidize electron-rich double bonds in biological molecules and macromolecules. For this reason, methylene blue has been used as a photosensitizer in the treatment of cancer and the protection of serum from viral agents. Methylene blue can be reactivated using energy from a light source in the body until processed out through the kidneys.

Timeline

Start

2020-10-12

Primary completion

2020-11-30

Completion

2020-12-30

Publications

• Background Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
• Background Ji W, Wang W, Zhao X, Zai J, Li X. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J Med Virol. 2020 Apr;92(4):433-440. doi: 10.1002/jmv.25682.
• Background Baud D, Qi X, Nielsen-Saines K, Musso D, Pomar L, Favre G. Real estimates of mortality following COVID-19 infection. Lancet Infect Dis. 2020 Jul;20(7):773. doi: 10.1016/S1473-3099(20)30195-X. Epub 2020 Mar 12. No abstract available.
• Background Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020. Euro Surveill. 2020 Feb;25(5):2000062. doi: 10.2807/1560-7917.ES.2020.25.5.2000062.
• Background Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020 May 12;323(18):1843-1844. doi: 10.1001/jama.2020.3786.
• Background Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of Methylene Blue in the nervous system. Med Res Rev. 2011 Jan;31(1):93-117. doi: 10.1002/med.20177.
• Background Bradberry SM. Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev. 2003;22(1):13-27. doi: 10.2165/00139709-200322010-00003.
• Background Barbosa P, Peters TM. The effects of vital dyes on living organisms with special reference to methylene blue and neutral red. Histochem J. 1971 Jan;3(1):71-93. doi: 10.1007/BF01686508. No abstract available.
• Background Wainwright M, Crossley KB. Methylene Blue--a therapeutic dye for all seasons? J Chemother. 2002 Oct;14(5):431-43. doi: 10.1179/joc.2002.14.5.431.
• Background Lee SK, Mills A. Novel photochemistry of leuco-Methylene Blue. Chem Commun (Camb). 2003 Sep 21;(18):2366-7. doi: 10.1039/b307228b.
• Background Khan S, Alam F, Azam A, Khan AU. Gold nanoparticles enhance methylene blue-induced photodynamic therapy: a novel therapeutic approach to inhibit Candida albicans biofilm. Int J Nanomedicine. 2012;7:3245-57. doi: 10.2147/IJN.S31219. Epub 2012 Jun 29.
• Background Wainwright M. Methylene blue derivatives--suitable photoantimicrobials for blood product disinfection? Int J Antimicrob Agents. 2000 Dec;16(4):381-94. doi: 10.1016/s0924-8579(00)00207-7.
• Background Tardivo JP, Del Giglio A, de Oliveira CS, Gabrielli DS, Junqueira HC, Tada DB, Severino D, de Fatima Turchiello R, Baptista MS. Methylene blue in photodynamic therapy: From basic mechanisms to clinical applications. Photodiagnosis Photodyn Ther. 2005 Sep;2(3):175-91. doi: 10.1016/S1572-1000(05)00097-9. Epub 2005 Nov 21.
• Background Tuite EM, Kelly JM. Photochemical interactions of methylene blue and analogues with DNA and other biological substrates. J Photochem Photobiol B. 1993 Dec;21(2-3):103-24. doi: 10.1016/1011-1344(93)80173-7.
• Background Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, Muller TH, Seltsam A. Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively. Transfusion. 2018 Sep;58(9):2202-2207. doi: 10.1111/trf.14652. Epub 2018 May 6.
• Background Chatterjee GC, Noltmann EA. Dye-sensitized photooxidation as a tool for the elucidation of critical amino acid residues in phosphoglucose isomerase. Eur J Biochem. 1967 Jul;2(1):9-18. doi: 10.1111/j.1432-1033.1967.tb00098.x. No abstract available.
• Background Triesscheijn M, Baas P, Schellens JH, Stewart FA. Photodynamic therapy in oncology. Oncologist. 2006 Oct;11(9):1034-44. doi: 10.1634/theoncologist.11-9-1034.
• Background Faddy HM, Fryk JJ, Hall RA, Young PR, Reichenberg S, Tolksdorf F, Sumian C, Gravemann U, Seltsam A, Marks DC. Inactivation of yellow fever virus in plasma after treatment with methylene blue and visible light and in platelet concentrates following treatment with ultraviolet C light. Transfusion. 2019 Jul;59(7):2223-2227. doi: 10.1111/trf.15332. Epub 2019 May 3.
• Background Fryk JJ, Marks DC, Hobson-Peters J, Watterson D, Hall RA, Young PR, Reichenberg S, Tolksdorf F, Sumian C, Gravemann U, Seltsam A, Faddy HM. Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light. Transfusion. 2017 Nov;57(11):2677-2682. doi: 10.1111/trf.14256. Epub 2017 Jul 17.
• Background Eickmann M, Gravemann U, Handke W, Tolksdorf F, Reichenberg S, Muller TH, Seltsam A. Inactivation of three emerging viruses - severe acute respiratory syndrome coronavirus, Crimean-Congo haemorrhagic fever virus and Nipah virus - in platelet concentrates by ultraviolet C light and in plasma by methylene blue plus visible light. Vox Sang. 2020 Apr;115(3):146-151. doi: 10.1111/vox.12888. Epub 2020 Jan 12.
• Background Ziv G, Heavner JE. Permeability of the blood-milk barrier to methylene blue in cows and goats. J Vet Pharmacol Ther. 1984 Mar;7(1):55-9. doi: 10.1111/j.1365-2885.1984.tb00879.x.
• Background Albert M, Lessin MS, Gilchrist BF. Methylene blue: dangerous dye for neonates. J Pediatr Surg. 2003 Aug;38(8):1244-5. doi: 10.1016/s0022-3468(03)00278-1.
• Background Sills MR, Zinkham WH. Methylene blue-induced Heinz body hemolytic anemia. Arch Pediatr Adolesc Med. 1994 Mar;148(3):306-10. doi: 10.1001/archpedi.1994.02170030076017.
• Background McFadyen I. The dangers of intra-amniotic methylene blue. Br J Obstet Gynaecol. 1992 Feb;99(2):89-90. doi: 10.1111/j.1471-0528.1992.tb14458.x. No abstract available.
• Background Dolk H. Methylene blue and atresia or stenosis of ileum and jejunum. EUROCAT Working Group. Lancet. 1991 Oct 19;338(8773):1021-2. doi: 10.1016/0140-6736(91)91885-x. No abstract available.
• Background van der Pol JG, Wolf H, Boer K, Treffers PE, Leschot NJ, Hey HA, Vos A. Jejunal atresia related to the use of methylene blue in genetic amniocentesis in twins. Br J Obstet Gynaecol. 1992 Feb;99(2):141-3. doi: 10.1111/j.1471-0528.1992.tb14473.x.
• Background Iyengar B, Lal SK. Methylene blue and organised differentiation in the chick embryo. Acta Anat (Basel). 1985;123(4):220-3. doi: 10.1159/000146005.
• Background Tiboni GM, Lamonaca D. Transplacental exposure to methylene blue initiates teratogenesis in the mouse: preliminary evidence for a mechanistic implication of cyclic GMP pathway disruption. Teratology. 2001 Oct;64(4):213-20. doi: 10.1002/tera.1066.

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Indications