Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, CHU Grenoble Alpes, TIMC, UMR5525, Grenoble, France.
Department of Pharmacy, Université Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France.
Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0057324. doi: 10.1128/aac.00573-24. Epub 2024 Jul 17.
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials.
This study is registered with ClinicalTrials.gov as NCT04633980.
由严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）大流行引发了一场严重的全球卫生危机，自 2019 年 11 月在中国首次发现以来，已报告数百万人死亡。免疫接种机会的全球差异强调了持续研究治疗干预措施的紧迫性。本研究专注于分子氢（H2）吸入作为 COVID-19 辅助治疗的潜在用途。H2 治疗在抑制与炎症相关的细胞内信号通路方面显示出前景，特别是在与鼻氧疗早期联合使用时。这项 I 期研究采用开放标签、前瞻性、单中心和单递增剂量设计，旨在评估已确诊 SARS-CoV-2 感染个体中该程序的安全性和耐受性。采用 3 + 3 设计，研究包括三个暴露持续时间（目标持续时间）：1 天（D1）、3 天（D2）和 6 天（D3）。我们得出的结论是，最大耐受持续时间至少为 3 天。每位患者均表现出对 H2 治疗的临床改善和良好耐受。据我们所知，这项 I 期临床试验是首次在住院 COVID-19 患者中建立吸入 H2（3.6%）和 N2（96.4%）混合物安全性的临床试验。所使用的原始设备和方法确保不存在爆炸风险。在纳入研究的 12 名患者中观察到的令人鼓舞的结果证明，通过更大规模的对照临床试验进一步探索是合理的。
本研究在 ClinicalTrials.gov 上注册为 NCT04633980。
