Ensaio aleatório - Reutilização de Ivermectina para tratamento COVID-19 de pacientes ambulatórios com doença leve em centros primários de saúde

Autores

DOI:

https://doi.org/10.33448/rsd-v11i8.30844

Palavras-chave:

COVID-19; Ivermectina; Assistência Ambulatorial; Reposicionamento de medicamentos; Atenção Primária à Saúde.

Resumo

Objetivo: avaliar a intervenção terapêutica com Ivermectina em pacientes ambulatoriais com doença leve de COVID-19, para aumentar a alta médica e prevenir a progressão para doença moderada ou grave.  Métodos: Ensaio Randomizado, n= 254. Os sujeitos foram divididos em grupo experimental (GE: n= 110) e grupo controle (GC: n= 144).  O GE recebeu Ivermectina oral 0,6 mg/kg de peso em duas doses.  Todos os participantes realizarão exame físico COVID-19 e diagnosticados com RT-PCR negativo no início e no final do protocolo.  As diferenças entre as variáveis ​​foram determinadas pelo teste Qui-quadrado (p<0,05).  O risco de contágio (Odds Ratio) foi calculado por meio do software STATA.  Resultados: Ambos os grupos foram semelhantes em idade, sexo e comorbidades.  Uma redução significativa no percentual de participantes com sintomas (PPS) foi observada no GE e GC quando a avaliação clínica dos sintomas foi realizada do 5º ao 9º (p= 0,0005).  Quando a avaliação clínica foi realizada do 10º ao 14º dia não houve diferença significativa.  Foi observada Maior proporção de alta médica no GE (98,2%) vs. GC (86,1%) (p= 0,0007).  O GE apresentou 8 vezes mais chance de receber alta médica do que o GC (OR 8,71, IC 95%: 1,99 – 38,12, p= 0,004).  O efeito do tratamento com Ivermectina para obter alta médica da assistência ambulatorial foi analisado pela regressão logística.  Então, a chance de obter alta médica foi independente das variáveis ​​sexo, idade e comorbidades.  Conclusão: Este trabalho apoia a eficácia potencial da Ivermectina na assistência ambulatorial com COVID-19 leve como uma intervenção potencialmente útil de saúde pública.

Referências

Ashburn, T. T. & Thor, K. B. (2004). Drug repositioning: identifying and developing new uses for existing drugs. Nature Reviews Drug Discovery [Internet].; 3(8):673–83. https://doi.org/10.1038/nrd1468

Bottan, N. L., Vera-Cossio, D. A., & Hoffmann, B. (2020). The unequal impact of the coronavirus pandemic: evidence of seventeen development countries [Internet]. https://publications.iadb.org/publications/english/document/The-Unequal-Impact-of-the-Coronavirus-Pandemic-Evidence-from-Seventeen-Developing-Countries.pdf

Bryant, A., Lawrie, T. A., Dowswell, T., Fordham, E. J., Mitchell, S., Hill, S. R., et al. (2021). Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. American Journal of Therapeutics. 28: e434–60. 10.1097/MJT.0000000000001442

Chaccour, C., Casellas, A., Blanco-Di Matteo, A., et al. (2021). The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial. EClinicalMedicine, 32:100720.

Chahla, R. E., Medina Ruiz, L., Ortega, E. S., et al. (2021). Prophylaxis Covid-19 in Healthcare Agents by Intensive Treatment with Ivermectin and Iota-carrageenan (Ivercar-Tuc). American Journal of Therapeutics, 28 (5). https://clinicaltrials.gov/ct2/show/NCT04701710?term=ivermectin&cond=Covid19&cntry=AR&city=Tucuman&draw=2&rank=1

Chahla, R. E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04784481#wrapper

Chahla, R. E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. Research Square. https://doi.org/10.21203/rs.3.rs-495945/v1

Chahla, R.E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. Research Square. https://doi.org/10.21203/rs.3.rs-495945/v2

Chahla, R. E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. medRxiv. https://www.medrxiv.org/content/medrxiv/early/2021/03/30/2021.03.29.21254554.full.pdf

Chahla, R. E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. medRxiv. https://www.medrxiv.org/content/10.1101/2021.03.29.21254554v1.full.pdf

Chahla, R. E., Medina Ruiz, L., Mena, T., et al. (2021). Cluster Randomised Trials – Ivermectin Repurposing for COVID-19 Treatment of Outpatient with Mild Disease in Primary Health Care Centers. medRxiv. https://www.medrxiv.org/content/10.1101/2021.03.29.21254554v1

Chong, C. R., & Sullivan, D. J. (2007). New uses for old drugs. Nature, 448(7154):645– https://doi.org/10.1038/448645a

Caly, L., Wagstaff, K. M., & Jans, D. A. (2012). Nuclear trafficking of proteins from RNA viruses: potential target for antivirals? Antiviral Research, 95(3):202–6.

Caly, L., Druce, J. D., Catton, M. G., Jans, D. A., & Wagsta, K. M. (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, 178:104787.

Carvallo, H., Hirsch, R., Alkis, P., & Contreras, V. (2020). Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel. Journal of Biomedical Research and Clinical Investigation, 2(1).

Carvallo, H., Hirsch, R., & Farinella, M. E. (2020). Safety and efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID 19. medRxiv the preprint server for health sciences; https://doi.org/10.1101/2020.09.10.20191619

Cassará, F. P. (2020). Ivermectina asociada a iota-Carragenina aplicada localmente en la cavidad bucal, en la profilaxis de la enfermedad COVID-19 en el personal de salud. Estudio IVERCAR01. 1–23.

Dyall, J., Coleman, C. M., Hart, B. J., et al. (2014). Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrobial Agents and Chemotherapy, 58(8):4885–93.

Edwards, G., Dingsdale, A., Helsby, N., Orme, M. L. E., & Breckenridge, A. M. (1988). The relative systemic availability of ivermectin after administration as capsule, tablet, and oral solution. European Journal of Clinical Pharmacology, 35:681– 4. 10.1007/BF00637608

Elgazzar, A., Hany, B., & Youssef, S. A. (2020). Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic. Research Square [Internet], 1–9. https://doi.org/10.21203/rs.3.rs-100956/v1

Krolewiecki, A., Lifschitz, A., Moragas, M., et al. (2020). Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial. SSRN Electronic Journal [Internet]. 10.2139/ssrn.3714649

Lima-Morales, R., Méndez-Hernández, P., Flores, Y. N., et al. (2021). Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico. International Journal of Infectious Diseases, 105: 598-605.

Liu, Z., Fang, H., Reagan, K., et al. (2013). In silico drug repositioning-what we need to know. Drug Discovery Today. Elsevier Ltd, 18: 110–5.

López-Medina, E., López, P., Hurtado, I. C., et al. (2021). Effect of Ivermectin on Time to Resolution of Symptoms Among Adults with Mild COVID-19: A Randomized Clinical Trial. Journal American Medical Association. 1–10. http://www.ncbi.nlm.nih.gov/pubmed/33662102

Marshall, J. C., Murthy, S., Diaz, J., et al. (2020). A minimal common outcome measure set for COVID-19 clinical research. Lancet Infectious Diseases, 20(8): e192–7.

Mayer, M. A., Krolewiecki, A., Ferrero, A., Bocchio, M., Barbero, J., Miguel, M., Paladini, A., Delgado, C., Ojeda, J. R., Elorza, C., Bertone, A., Fleitas, P. E., Vera, G., & Kohan, M. R. (2022) Safety and Efficacy of a MEURI Program for the Use of High Dose Ivermectin in COVID-19 Patients. Frontiers in Public Health, 10:813378. 10.3389/fpubh.2022.813378

Ministerio de Salud de la Nación Argentina. Criteria for defining COVID-19 cases [Internet]. 2020. https://www.argentina.gob.ar/salud/coronavirus- COVID-19/definicion-de-caso

Ministerio de Salud Pública de la Provincia de Tucumán. Protocolo de Investigación I.D.D.E.A - TUC. 2020. https://msptucuman.gov.ar/wordpress/wp-content/uploads/2020/10/SPROTOCOLO-DE-INV-IDDEA.pdf

Neil, M., Fenton, N., Kow, C. S., Hasan, S. S., Popp, M., Stegemann, M., et al. (2021). Bayesian hypothesis testing and hierarchical modeling of ivermectin effectiveness. American Journal of Therapeutics. 28:CD015017. 10.1097/MJT.0000000000001450

Osterberg, L., & Blaschke, T. (2005). Adherence to Medication. The New England Journal of Medicine, 353(5):487–97.

Padhi, S., Pati, A., & Panda, A. K. (2021). Effect of ivermectin in the treatment of COVID-19: a trial sequential analysis highlighted the requirement of additional randomized controlled trials. Clinical Infectious Diseases. ciab692. 10.1093/cid/ciab692

Rodríguez Chamorro, MÁ., García-Jiménez, E., Amariles, P., Rodríguez Chamorro, A., & Faus, M. J. (2008). Revisión de tests de medición del cumplimiento terapéutico utilizados en la práctica clínica. Atención primaria, 40(8):413–7. 10.1157/13125407

Roman, Y. M., Burela, P. A., Pasupuleti, V., Piscoya, A., Vidal, J. E., & Hernandez, A. V. (2021). Ivermectin for the treatment of COVID-19: a systematic review and meta-analysis of randomized controlled trials. Clinical of Infectious Diseases. 10.1101/2021.05.21.21257595

Rubin, J. E., & Crowe, S. E. (2020). COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Annals of Internal Medicine, 172(1): ITC1–14.

WHO-adverse reaction terminology (WHO-ART). In: Dictionary of Pharmaceutical Medicine. Springer Vienna; 2009. p. 192–3.

World Health Organization (WHO). Ethical issues related to study design for trials on therapeutics for Ebola Virus Disease. WHO Ethics Work Gr Meet. (2014) 1–7.

WHO. What we know about long-term effects of COVID-19. The latest on the COVID- 19 global situation and long-term sequelae. 2020; (September). https://www.who.int/docs/default-source/coronaviruse/risk-comms-updates/update-36- long-term-symptoms.pdf?sfvrsn=5d3789a6_2

Wu, Z., & Mc Googan, J. M. (2020). Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. Journal American Medical Association, 323(13):1239–42.

Zhou, F., Yu, T., Du, R., et al. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 395(10229):1054–62. http://dx.doi.org/10.1016/S0140-6736(20)30566-3

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21/06/2022

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CHAHLA, R. E.; RUIZ, L. M. .; MENA, T. .; BREPE, Y.; TERRANOVA, P.; ORTEGA, E. S.; BARRENECHEA, G. G.; GOROSO, D. G.; PERAL DE BRUNO, M. de los Ángeles. Ensaio aleatório - Reutilização de Ivermectina para tratamento COVID-19 de pacientes ambulatórios com doença leve em centros primários de saúde. Research, Society and Development, [S. l.], v. 11, n. 8, p. e35511830844, 2022. DOI: 10.33448/rsd-v11i8.30844. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/30844. Acesso em: 19 maio. 2024.

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Ciências da Saúde