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Clinical Trial
. 2024 Aug 27;14(1):19902.
doi: 10.1038/s41598-024-70064-8.

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

Vinicius Tadeu Ramos da Silva Grillo  1 , Matheus Bertanha  2   3 , Lenize da Silva Rodrigues  1   4 , Marcelo Andrade de Lima  5 , Pedro Luciano Mellucci Filho  1 , Rafael Rahal Guaragna Machado  6 , Edson Luiz Durigon  6   7 , Nathália Dias Sertorio  1 , Marjorie de Assis Golim  4 , Andrei Moroz  8 , Aline Márcia Marques Braz  4 , Leonardo Nazário de Moraes  4 , Marco Antonio Leite  9 , Helena Bonciani Nader  10 , Gustavo Constantino de Campos  11 , Cristiane Rodrigues Guzzo Carvalho  6 , Fábio Florença Cardoso  12 , Angelo José Magro  12 , Helga Caputo Nunes  13 , Rejane Maria Tommasini Grotto  4   14 , Rita de Cássia Alvarado  4 , Maria Inês de Moura Campos Pardini  15 , Marcone Lima Sobreira  1 , Erika Alessandra Pellison Nunes da Costa  16 , Alexandre Naime Barbosa  16 , Carlos Magno Castelo Branco Fortaleza  16
Affiliations
Clinical Trial

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

Vinicius Tadeu Ramos da Silva Grillo et al. Sci Rep. .

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.

Keywords: COVID-19; Enriched heparin; SARS-CoV-2; Safety; Treatment.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Enriched heparin inhibits SARS-CoV-2 infection in Vero cells. (A) Percentage of virus load inhibition in the supernatant of cells infected with SARS-CoV-2 (102 TCID50/mL) cultured with increasing enriched heparin concentration (up to 250 ug/ml) for 72 h. (B) Three different times of heparin addition were evaluated, comprising the virus absorption (AD), post-infection (PI), and adsorption plus post-infection (FT). Data are representative of mean (SEM) of 4 replicates from 2 independent experiments. Data were analysed using Two-Way ANOVA with Dunnett’s multiple comparisons test. *p < 0.05; **p < 0.01.
Figure 2
Figure 2
Study Flow Diagram.
See this image and copyright information in PMC

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