H2 inhalation therapy in patients with moderate Covid 19 (H2 COVID) : a prospective ascending-dose phase 1 clinical trial

Introduction: The 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. Methods: 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). Results: We concluded that the Maximum Tolerated Duration is at least three days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. Discussion/conclusion: To the best of our knowledge, this phase 1 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04633980 ### Clinical Protocols ### Funding Statement The H2COVID study was supported by AirProducts which kindly provided the cylinders with the gas mixture and the administration device. It was carried out at CHU Grenoble Alpes (Grenoble University Hospital, France). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by French National Agency for Drug Safety and has been approved by a personal protection committee (SUD MED IV) on November 10th 2020 (Reference : 20 10 12-covid), following french regulation. Ethical approval was given. The clinical trial is available on clinicaltrials.gov with identifier [NCT04633980][1]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04633980&atom=%2Fmedrxiv%2Fearly%2F2024%2F03%2F19%2F2024.03.15.24304071.atom