Inhaled nebulised unfractionated heparin (UFH) for the treatment of hospitalised patients with COVID-19: A randomised controlled pilot study

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics Pub Date : 2023-06-01 DOI:10.1016/j.pupt.2023.102212

Gilberto DeNucci , Tom Wilkinson , Carlos Sverdloff , Tainah Babadopulos , Ashley Woodcock , Jan Shute , Pedro Renato Guazelli , Luis Frederico Gerbase , Paulo A.S. Mourão , Dave Singh , Frank M.P. van Haren , Clive Page

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引用次数: 1

Abstract

There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in treating patients with COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted to two hospitals in Brazil. One hundred patients were planned to be randomised to either “standard of care” (SOC) or SOC plus nebulized UFH. The trial was stopped after randomisation of 75 patients due to falling COVID-19 hospitalisation rates. Significance tests were 1-sided test (10% significance level). The key analysis populations were intention to treat (ITT) and modified ITT (mITT) which excluded (from both arms) subjects admitted to ITU or who died within 24 h of randomisation.

In the ITT population (n = 75), mortality was numerically lower for nebulised UFH (6 out of 38 patients; 15.8%) versus SOC (10 out of 37 patients; 27.0%), but not statistically significant; odds ratio (OR) 0.51, p = 0.24. However, in the mITT population, nebulised UFH reduced mortality (OR 0.2, p = 0.035).

Length of hospital stay was similar between groups, but at day 29, there was a greater improvement in ordinal score following treatment with UFH in the ITT and mITT populations (p = 0.076 and p = 0.012 respectively), while mechanical ventilation rates were lower with UFH in the mITT population (OR 0.31; p = 0.08). Nebulised UFH did not cause any significant adverse events. In conclusion, nebulised UFH added to SOC in hospitalised patients with COVID-19 was well tolerated and showed clinical benefit, particularly in patients who received at least 6 doses of heparin.

This trial was funded by The J.R. Moulton Charity Trust and registered under REBEC RBR-8r9hy8f (UTN code: U1111-1263-3136).

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吸入雾化未分离肝素(UFH)治疗COVID-19住院患者:一项随机对照试点研究

使用雾化普通肝素（UFH）治疗新冠肺炎患者有很强的科学依据。这项试点研究调查了雾化UFH在治疗新冠肺炎住院患者时是否安全，是否对死亡率、住院时间和临床进展有任何影响。这项平行组、开放标签、随机试验包括巴西两家医院收治的确诊感染严重急性呼吸系统综合征冠状病毒2型的成年患者。计划将100名患者随机分为“标准护理”（SOC）或SOC加雾化UFH。由于新冠肺炎住院率下降，对75名患者进行随机分组后，试验停止。显著性检验为单侧检验（10%显著性水平）。关键分析人群是意向治疗（ITT）和改良ITT（mITT），它们排除了（双臂）接受ITU或在随机分组后24小时内死亡的受试者。在ITT人群（n=75）中，雾化不明飞行物的死亡率（38名患者中有6名；15.8%）低于SOC（37名患者中的10名；27.0%），但无统计学意义；比值比（OR）0.51，p=0.24。然而，在mITT人群中，雾化不明飞行物降低了死亡率（OR 0.2，p=0.035）。两组之间的住院时间相似，但在第29天，ITT和mITT人群接受不明飞行物治疗后的顺序得分有了更大的改善（分别为p=0.076和p=0.012），而在mITT人群中，UFH的机械通气率较低（OR 0.31；p=0.08）。雾化UFH没有引起任何显著的不良事件。总之，添加到新冠肺炎住院患者SOC中的雾化UFH具有良好的耐受性，并显示出临床益处，尤其是在接受至少6剂肝素的患者中。该试验由J.R.莫尔顿慈善信托基金资助，并在REPEC RBR-8r9hy8f（UTN代码：U1111-1263-3136）下注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pulmonary pharmacology & therapeutics 医学-呼吸系统

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

42 days

期刊介绍： Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.