Hinhalation therapy in patients with moderate COVID-19 (HCOVID): a prospective ascending-dose phase I clinical trial.
中等症COVID-19患者における水素吸入の安全性・忍容性を評価するフェーズI用量漸増臨床試験（HCOVID）
Abstract
This phase I open-label, prospective, monocentric, single ascending-dose trial investigated the safety and tolerability of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized patients with confirmed SARS-CoV-2 infection. Using a 3+3 design, three exposure durations were evaluated: 1 day, 3 days, and 6 days. All 12 enrolled patients demonstrated clinical improvement and excellent tolerability. The maximum tolerated duration was determined to be at least 3 days. The device used was specifically designed to eliminate explosion risk. H2 inhalation was explored as an adjunctive approach alongside nasal oxygen delivery, with interest in its potential to modulate inflammation-related intracellular signaling. The authors report this as the first clinical trial to establish the safety profile of this H2/N2 mixture in COVID-19 patients, and suggest that the findings support progression to larger controlled trials. The study is registered at ClinicalTrials.gov (NCT04633980).
Mechanism
H2 inhalation is proposed to suppress intracellular signaling pathways associated with inflammatory responses, potentially reducing COVID-19-related inflammation when administered early alongside oxygen supplementation.
Bibliographic
- Authors
- Salomez-Ihl C, Giai J, Barbado M, Paris A, Touati S, Alcaraz JP, et al.
- Journal
- Antimicrob Agents Chemother
- Year
- 2024 (2024-08-07)
- PMID
- 39016593
- DOI
- 10.1128/aac.00573-24
- PMC
- PMC11304737
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
See also: