BMC Pulm Med . Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospita

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BMC Pulm Med


. 2025 Jul 22;25(1):346.
doi: 10.1186/s12890-025-03824-5. Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospitalised patients with COVID-19 pneumonia: a randomized controlled clinical trial​

Junhui Gong[SUP] #[/SUP][SUP] 1 [/SUP], Naifu Nie[SUP] #[/SUP][SUP] 1 [/SUP], Minrui Jiang[SUP] #[/SUP][SUP] 2 [/SUP], Xinyu Yang[SUP] 1 [/SUP], Qinghua Wang[SUP] 3 [/SUP], Jia Deng[SUP] 1 [/SUP], Jun Kang[SUP] 1 [/SUP], Xin Li[SUP] 1 [/SUP], Li Zhang[SUP] 1 [/SUP], Ying Zhang[SUP] 1 [/SUP], Nuo Luo[SUP] 1 [/SUP], Xiaoyi Du[SUP] 1 [/SUP], Ling Wang[SUP] 1 [/SUP], Wei Zhou[SUP] 1 [/SUP], Hui Cao[SUP] 2 [/SUP], Kunlin Li[SUP] 4 [/SUP], Guoqiang Cao[SUP] 5 [/SUP], Li Li[SUP] 6 [/SUP]



Affiliations

• PMID: 40696325
• DOI: 10.1186/s12890-025-03824-5

Abstract

Background: Promoting the absorption of COVID-19 pneumonia is critical for reducing pulmonary sequelae and improving prognosis. This study aimed to evaluate the efficacy and safety of nebulized unfractionated heparin, acetylcysteine, budesonide, and ipratropium bromide (HABIT) in hospitalized patients with COVID-19 pneumonia.
Methods: This single-center, open-label, randomized, parallel-group trial was conducted at a tertiary hospital in China. Participants were randomized 1:1 to receive either standard of care (SOC) or SOC plus nebulized HABIT. The HABIT protocol included daily quadruple nebulization for seven days, comprising 6000 units heparin sodium, 2 mg budesonide, 0.3 g acetylcysteine, and 0.5 mg ipratropium bromide. The primary outcome was the change in lung lesions assessed by chest CT scans on admission (Day 0) and post-treatment (Day 8).
Results: A total of 74 patients were randomized to the HABIT group (n = 37) or the control group (n = 37). Four patients per group were excluded during follow-up, leaving 66 patients for final analysis. Baseline CT scores were comparable between groups (10.55 ± 3.11 vs. 10.76 ± 2.85, p = 0.774). Post-treatment, the HABIT group showed significantly lower mean CT scores (6.6 ± 2.98 vs. 8.69 ± 2.53, p = 0.003) and greater lesion absorption (37.5% vs. 20%, p < 0.001) compared to controls. The HABIT group also exhibited a non-significant improvement in PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] (75.27 vs. 51.23, p = 0.113). Safety analysis showed no significant differences in activated partial thromboplastin time or serious adverse events.
Conclusion: The adjunctive HABIT regimen demonstrates favorable efficacy and safety in treating COVID-19 pneumonia.
Trial registration: The clinical trial was registered with the Chinese Clinical Trial Registry (ChiCTR; www.chictr.org.cn ; ID: ChiCTR2300073871) on July 24, 2023. Ethical approval was valid from May 2023 to May 2025.

Keywords: CT severity scores; Corona virus disease 2019 (COVID-19); Nebulization therapy; Pathophysiology; Unfractionated heparin; Viral pneumonia.

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