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Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial

  • Authors:
    • Ivan Delgado‑Enciso
    • Juan Paz‑Garcia
    • Carlos E. Barajas‑Saucedo
    • Karen A. Mokay‑Ramírez
    • Carmen Meza‑Robles
    • Rodrigo Lopez‑Flores
    • Marina Delgado‑Machuca
    • Efren Murillo‑Zamora
    • Jose A. Toscano‑Velazquez
    • Josuel Delgado‑Enciso
    • Valery Melnikov
    • Mireya Walle‑Guillen
    • Hector R. Galvan‑Salazar
    • Osiris G. Delgado‑Enciso
    • Ariana Cabrera‑Licona
    • Eduardo J. Danielewicz‑Mata
    • Pablo J. Mandujano‑Diaz
    • José Guzman‑Esquivel
    • Daniel A. Montes‑Galindo
    • Henry Perez‑Martinez
    • Jesus M. Jimenez‑Villegaz
    • Alejandra E. Hernandez‑Rangel
    • Patricia Montes‑Diaz
    • Iram P. Rodriguez‑Sanchez
    • Margarita L. Martinez‑Fierro
    • Idalia Garza‑Veloz
    • Daniel Tiburcio‑Jimenez
    • Sergio A. Zaizar‑Fregoso
    • Fidadelfo Gonzalez‑Alcaraz
    • Laydi Gutierrez‑Gutierrez
    • Luciano Diaz‑Lopez
    • Mario Ramirez‑Flores
    • Hannah P. Guzman‑Solorzano
    • Gustavo Gaytan‑Sandoval
    • Carlos R. Martinez‑Perez
    • Francisco Espinoza‑Gómez
    • Fabián Rojas‑Iarios
    • Michael J. Hirsch‑Meillon
    • Luz M. Baltazar-Rodriguez
    • Enrique Barrios‑Navarro
    • Vladimir Oviedo‑Rodriguez
    • Martha A. Mendoza‑Hernandez
    • Emilio Prieto‑Diaz‑Chavez
    • Brenda A. Paz‑Michel
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, México, Department of Internal Medicine and Surgery, Union Hospital Center, Villa de Álvarez, Colima 28970, México, Department of Research, Cancerology State Institute, Colima State Health Services, Colima 28085, México, Department of Research, General Hospital of Zone No. 1 and Family Medicine Unit No. 19 IMSS, Villa de Alvarez, Colima 28984, México, Department of Research, Foundation for Cancer Ethics, Education and Research of the Cancerology State Institute, Colima 28085, México, Department of Research, Esteripharma S.A. de C.V., Ciudad de México 03100, México, COVID‑19 Respiratory Care Clinic INSABI Poliforum, Tuxtla Gutierrez, Chiapas 29040, México, Private Medical Office Xochitepec, Xochitepec, Morelos 62795, México, Laboratory of Molecular and Structural Physiology, School of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolas de los Garza, Nuevo León 66455, México, Molecular Medicine Laboratory, Academic Unit of Human Medicine and Health Sciences, Autonomous University of Zacatecas, Zacatecas 98160, México
    Copyright: © Delgado‑Enciso et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 915
    |
    Published online on: June 29, 2021
       https://doi.org/10.3892/etm.2021.10347
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Abstract

Coronavirus disease 2019 (COVID‑19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID‑19. A prospective, 2‑arm, parallel‑group, randomized, open‑label, multi‑center, phase I‑II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20‑day follow‑up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro‑pharyngeal detection by reverse transcription‑quantitative (RT‑q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03‑0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01‑0.42, P=0.007) and also resulted in an 18‑fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29‑45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT‑qPCR in naso/oro‑pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C‑reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone‑cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID‑19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX‑COVID19: RPCEC00000309).
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Copy and paste a formatted citation
Spandidos Publications style
Delgado‑Enciso I, Paz‑Garcia J, Barajas‑Saucedo CE, Mokay‑Ramírez KA, Meza‑Robles C, Lopez‑Flores R, Delgado‑Machuca M, Murillo‑Zamora E, Toscano‑Velazquez JA, Delgado‑Enciso J, Delgado‑Enciso J, et al: Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial. Exp Ther Med 22: 915, 2021.
APA
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C.E., Mokay‑Ramírez, K.A., Meza‑Robles, C., Lopez‑Flores, R. ... Paz‑Michel, B.A. (2021). Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial. Experimental and Therapeutic Medicine, 22, 915. https://doi.org/10.3892/etm.2021.10347
MLA
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C. E., Mokay‑Ramírez, K. A., Meza‑Robles, C., Lopez‑Flores, R., Delgado‑Machuca, M., Murillo‑Zamora, E., Toscano‑Velazquez, J. A., Delgado‑Enciso, J., Melnikov, V., Walle‑Guillen, M., Galvan‑Salazar, H. R., Delgado‑Enciso, O. G., Cabrera‑Licona, A., Danielewicz‑Mata, E. J., Mandujano‑Diaz, P. J., Guzman‑Esquivel, J., Montes‑Galindo, D. A., Perez‑Martinez, H., Jimenez‑Villegaz, J. M., Hernandez‑Rangel, A. E., Montes‑Diaz, P., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L., Garza‑Veloz, I., Tiburcio‑Jimenez, D., Zaizar‑Fregoso, S. A., Gonzalez‑Alcaraz, F., Gutierrez‑Gutierrez, L., Diaz‑Lopez, L., Ramirez‑Flores, M., Guzman‑Solorzano, H. P., Gaytan‑Sandoval, G., Martinez‑Perez, C. R., Espinoza‑Gómez, F., Rojas‑Iarios, F., Hirsch‑Meillon, M. J., Baltazar-Rodriguez, L. M., Barrios‑Navarro, E., Oviedo‑Rodriguez, V., Mendoza‑Hernandez, M. A., Prieto‑Diaz‑Chavez, E., Paz‑Michel, B. A."Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial". Experimental and Therapeutic Medicine 22.3 (2021): 915.
Chicago
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C. E., Mokay‑Ramírez, K. A., Meza‑Robles, C., Lopez‑Flores, R., Delgado‑Machuca, M., Murillo‑Zamora, E., Toscano‑Velazquez, J. A., Delgado‑Enciso, J., Melnikov, V., Walle‑Guillen, M., Galvan‑Salazar, H. R., Delgado‑Enciso, O. G., Cabrera‑Licona, A., Danielewicz‑Mata, E. J., Mandujano‑Diaz, P. J., Guzman‑Esquivel, J., Montes‑Galindo, D. A., Perez‑Martinez, H., Jimenez‑Villegaz, J. M., Hernandez‑Rangel, A. E., Montes‑Diaz, P., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L., Garza‑Veloz, I., Tiburcio‑Jimenez, D., Zaizar‑Fregoso, S. A., Gonzalez‑Alcaraz, F., Gutierrez‑Gutierrez, L., Diaz‑Lopez, L., Ramirez‑Flores, M., Guzman‑Solorzano, H. P., Gaytan‑Sandoval, G., Martinez‑Perez, C. R., Espinoza‑Gómez, F., Rojas‑Iarios, F., Hirsch‑Meillon, M. J., Baltazar-Rodriguez, L. M., Barrios‑Navarro, E., Oviedo‑Rodriguez, V., Mendoza‑Hernandez, M. A., Prieto‑Diaz‑Chavez, E., Paz‑Michel, B. A."Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial". Experimental and Therapeutic Medicine 22, no. 3 (2021): 915. https://doi.org/10.3892/etm.2021.10347
Copy and paste a formatted citation
x
Spandidos Publications style
Delgado‑Enciso I, Paz‑Garcia J, Barajas‑Saucedo CE, Mokay‑Ramírez KA, Meza‑Robles C, Lopez‑Flores R, Delgado‑Machuca M, Murillo‑Zamora E, Toscano‑Velazquez JA, Delgado‑Enciso J, Delgado‑Enciso J, et al: Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial. Exp Ther Med 22: 915, 2021.
APA
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C.E., Mokay‑Ramírez, K.A., Meza‑Robles, C., Lopez‑Flores, R. ... Paz‑Michel, B.A. (2021). Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial. Experimental and Therapeutic Medicine, 22, 915. https://doi.org/10.3892/etm.2021.10347
MLA
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C. E., Mokay‑Ramírez, K. A., Meza‑Robles, C., Lopez‑Flores, R., Delgado‑Machuca, M., Murillo‑Zamora, E., Toscano‑Velazquez, J. A., Delgado‑Enciso, J., Melnikov, V., Walle‑Guillen, M., Galvan‑Salazar, H. R., Delgado‑Enciso, O. G., Cabrera‑Licona, A., Danielewicz‑Mata, E. J., Mandujano‑Diaz, P. J., Guzman‑Esquivel, J., Montes‑Galindo, D. A., Perez‑Martinez, H., Jimenez‑Villegaz, J. M., Hernandez‑Rangel, A. E., Montes‑Diaz, P., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L., Garza‑Veloz, I., Tiburcio‑Jimenez, D., Zaizar‑Fregoso, S. A., Gonzalez‑Alcaraz, F., Gutierrez‑Gutierrez, L., Diaz‑Lopez, L., Ramirez‑Flores, M., Guzman‑Solorzano, H. P., Gaytan‑Sandoval, G., Martinez‑Perez, C. R., Espinoza‑Gómez, F., Rojas‑Iarios, F., Hirsch‑Meillon, M. J., Baltazar-Rodriguez, L. M., Barrios‑Navarro, E., Oviedo‑Rodriguez, V., Mendoza‑Hernandez, M. A., Prieto‑Diaz‑Chavez, E., Paz‑Michel, B. A."Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial". Experimental and Therapeutic Medicine 22.3 (2021): 915.
Chicago
Delgado‑Enciso, I., Paz‑Garcia, J., Barajas‑Saucedo, C. E., Mokay‑Ramírez, K. A., Meza‑Robles, C., Lopez‑Flores, R., Delgado‑Machuca, M., Murillo‑Zamora, E., Toscano‑Velazquez, J. A., Delgado‑Enciso, J., Melnikov, V., Walle‑Guillen, M., Galvan‑Salazar, H. R., Delgado‑Enciso, O. G., Cabrera‑Licona, A., Danielewicz‑Mata, E. J., Mandujano‑Diaz, P. J., Guzman‑Esquivel, J., Montes‑Galindo, D. A., Perez‑Martinez, H., Jimenez‑Villegaz, J. M., Hernandez‑Rangel, A. E., Montes‑Diaz, P., Rodriguez‑Sanchez, I. P., Martinez‑Fierro, M. L., Garza‑Veloz, I., Tiburcio‑Jimenez, D., Zaizar‑Fregoso, S. A., Gonzalez‑Alcaraz, F., Gutierrez‑Gutierrez, L., Diaz‑Lopez, L., Ramirez‑Flores, M., Guzman‑Solorzano, H. P., Gaytan‑Sandoval, G., Martinez‑Perez, C. R., Espinoza‑Gómez, F., Rojas‑Iarios, F., Hirsch‑Meillon, M. J., Baltazar-Rodriguez, L. M., Barrios‑Navarro, E., Oviedo‑Rodriguez, V., Mendoza‑Hernandez, M. A., Prieto‑Diaz‑Chavez, E., Paz‑Michel, B. A."Safety and efficacy of a COVID‑19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open‑label, controlled trial". Experimental and Therapeutic Medicine 22, no. 3 (2021): 915. https://doi.org/10.3892/etm.2021.10347
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