Australian National University, College of Health and Medicine, Canberra, Australia.
Faculty of Health, University of Canberra, Canberra, Australia.
Br J Clin Pharmacol. 2021 Aug;87(8):3075-3091. doi: 10.1111/bcp.14714. Epub 2021 Jan 19.
Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis.
The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes.
We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn.
TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.
雾化吸入未分级肝素（UFH）具有强有力的科学和生物学依据，因此迫切需要研究其在 COVID-19 患者中的治疗潜力。UFH 具有抗病毒作用，并可阻止 SARS-CoV-2 病毒进入哺乳动物细胞。此外，UFH 还具有显著的抗炎和抗凝特性，可限制肺损伤和血管性肺血栓形成的进展。
正在进行的 INHALE-HEP 试验是一项针对住院 COVID-19 患者的雾化吸入未分级肝素治疗的前瞻性个体患者数据分析，为正在进行的随机对照试验和早期阶段研究的荟萃分析。各研究均在多个国家进行。参与研究的患者均为确诊 SARS-CoV-2 感染且无需立即机械通气的成年住院患者，随机分配至雾化吸入 UFH 组或标准治疗组。所有研究均收集最小核心数据集。该荟萃分析的主要结局为 28 天内插管（或死亡，对于在插管前死亡的患者）。次要结局为氧合、临床恶化和死亡率，采用时间事件分析进行评估。个别研究可能有其他结局。
我们采用贝叶斯监测方法，随后进行个体患者数据、结局和不良事件的分析。所有分析均遵循意向治疗原则，将所有参与者纳入至其接受治疗的治疗组，除非失访或退出。
试验注册、伦理和传播：该荟萃分析在 ClinicalTrials.gov 注册，ID 为 NCT04635241。每个参与研究均单独注册，并获得了相关伦理委员会或机构审查委员会的批准。本研究的结果将与世界卫生组织共享，发表在科学期刊上，并在科学会议上展示。
