# Molecular Hydrogen for Outpatients with COVID-19 (Hydro-COVID): A Phase 3 Randomised, Triple-Blinded, Pragmatic, Placebo-Controlled, Multicentre Trial.
> 外来COVID-19患者における水素富化水の有効性と安全性：第3相無作為化三重盲検プラセボ対照多施設試験（Hydro-COVID）


## Abstract

This phase 3, triple-blind, randomised, placebo-controlled multicentre trial enrolled 675 outpatients with laboratory-confirmed mild-to-moderate COVID-19. Participants were assigned to receive hydrogen-rich water (HRW) or placebo twice daily for 21 days, initiated within 5 days of symptom onset. The primary endpoint was clinical worsening by day 14. Clinical worsening occurred in 46.1% of the HRW group versus 43.5% in the placebo group (hazard ratio 1.09; 90% CI 0.90–1.31), indicating no superiority of HRW over placebo. One death was recorded in the HRW group and two in the placebo group by day 30. Adverse events were reported in 27% and 26.2% of participants in the HRW and placebo groups, respectively, with no meaningful difference in safety profiles between arms. The study concludes that HRW administered twice daily for 21 days did not reduce the risk of clinical deterioration in this patient population.

### Mechanism

Molecular hydrogen was hypothesised to mitigate COVID-19 progression through its antioxidant, anti-inflammatory, and anti-apoptotic properties, potentially suppressing oxidative stress and inflammatory cascades; however, no significant clinical benefit was demonstrated in this trial.

## Bibliographic

- **Authors**: Gaboreau Y, Milovančev A, Rolland C, Eychenne C, Alcaraz JP, Ihl C, et al.
- **Journal**: J Clin Med
- **Year**: 2024 (2024-07-24)
- **PMID**: [39124575](https://pubmed.ncbi.nlm.nih.gov/39124575/)
- **DOI**: [10.3390/jcm13154308](https://doi.org/10.3390/jcm13154308)
- **PMC**: [PMC11313273](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11313273/)
- **Study type**: human randomized controlled trial
- **Delivery route**: hydrogen-rich water
- **Effect reported**: null

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 39124575. https://h2-papers.org/en/papers/39124575
> **Source**: PubMed PMID [39124575](https://pubmed.ncbi.nlm.nih.gov/39124575/)