H2inhalation therapy in patients with moderate Covid 19 (H2COVID): a prospective ascending-dose phase 1 clinical trial

Abstract

AbstractIntroductionThe 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.MethodsThis 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).ResultsWe concluded that the Maximum Tolerated Duration is at least three days. Every patient showed clinical improvement and excellent tolerance to H2 therapy.Discussion/conclusionTo 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.QuestionWhat is the Maximum Tolerated Duration of inhalation for a gaseous mixture including 3.6% of molecular dihydrogen in moderate COVID-19 patients?FindingsThe Maximum Tolerated Duration is at least three days. All patients showed clinical improvement and excellent tolerance to H2 therapy. 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.MeaningA gaseous mixture including 3.6% H2, considered in the literature to have promising anti-inflammatory potential, and presenting no risk of explosion, can be used in patients with moderate COVID 19 for at least three days.