Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial

Ramos da Silva Grillo, Vinicius Tadeu; Bertanha, Matheus; da Silva Rodrigues, Lenize; de Lima, Marcelo Andrade; Mellucci Filho, Pedro Luciano; Rahal Guaragna Machado, Rafael; Durigon, Edson Luiz; Dias Sertorio, Nathália; de Assis Golim, Marjorie; Moroz, Andrei; Marques Braz, Aline Márcia; de Moraes, Leonardo Nazário; Leite, Marco Antonio; Bonciani Nader, Helena; de Campos, Gustavo Constantino; Rodrigues Guzzo Carvalho, Cristiane; Florença Cardoso, Fábio; Magro, Angelo José; Caputo Nunes, Helga; Tommasini Grotto, Rejane Maria; de Cássia Alvarado, Rita; de Moura Campos Pardini, Maria Inês; Lima Sobreira, Marcone; da Costa, Erika Alessandra Pellison Nunes; Naime Barbosa, Alexandre; Fortaleza, Carlos Magno Castelo Branco

Abstract

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Citation

Ramos da Silva Grillo, V. T., Bertanha, M., da Silva Rodrigues, L., de Lima, M. A., Mellucci Filho, P. L., Rahal Guaragna Machado, R., Durigon, E. L., Dias Sertorio, N., de Assis Golim, M., Moroz, A., Marques Braz, A. M., de Moraes, L. N., Leite, M. A., Bonciani Nader, H., de Campos, G. C., Rodrigues Guzzo Carvalho, C., Florença Cardoso, F., Magro, A. J., Caputo Nunes, H., Tommasini Grotto, R. M., …Fortaleza, C. M. C. B. (in press). Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial. Scientific Reports, 14(1), Article 19902. https://doi.org/10.1038/s41598-024-70064-8

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2024
• Online Publication Date: Aug 27, 2024
• Deposit Date: Sep 2, 2024
• Publicly Available Date: Sep 2, 2024
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 19902
• DOI: https://doi.org/10.1038/s41598-024-70064-8
• Keywords: Enriched heparin, Treatment, COVID-19, Safety, SARS-CoV-2
• Public URL: https://keele-repository.worktribe.com/output/889932
• Publisher URL: https://www.nature.com/articles/s41598-024-70064-8